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Item 7. Management’s Discussion and Analysis

2023-02-28 compared with 2022-03-29 · 152 added, 118 removed, 164 unchanged (62% of the section changed)

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This section under Management’s Discussion and Analysis of Financi al Condition and Results of Operations generally discusses 2022 and 2021 items and year-to-year comparisons between 2022 and 2021.

Discussions of 2019 items and year-to-year comparisons between 2020 and 2019 that are not included in this Annual Report on Form 10-K can be found in the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in the prospectus we filed with the SEC pursuant to Rule 424(b)(4) under the Securities Act of 1933, as amended, on June 21, 2021.

We are a T-cell reprogramming company dedicated to the mastery of T cells to cure patients with solid tumors.

We believe the key to effective cell therapy is the mastery of the identity, fate and function of cells to create living medicines.

We take a systematic, interrogative, cell biology-driven approach to overcome what we view as the two major barriers to successful ACT – (1) T-cell exhaustion and (2) lack of durable stemness – through the application of our proprietary ex vivo genetic and epigenetic reprogramming technologies, Gen-R™ and Epi-R™.

Our technologies are designed to be applied in a target and modality agnostic manner to chimeric antigen receptor (CAR), tumor-infiltrating lymphocytes (TIL) and T-cell receptor (TCR) therapies to fundamentally improve the properties of T cells needed to eradicate solid tumors.

We believe our autologous T-cell therapies will generate improved, durable clinical outcomes that are potentially curative for patients with solid tumors.

We are building a multi-modality product pipeline across several solid tumor indications with high unmet needs.

We are advancing a product pipeline of promising living cell product candidates across multiple ACT modalities that incorporate our Gen-R and Epi-R technology platforms.

Discussions of 2020 items and year-to-year comparisons between 2021 and 2020 that are not included in this Annual Report on Form 10-K can be found in the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K for the fiscal year ended December 31, 2021.

We are a clinical-stage cell therapy company advancing a pipeline of product candidates for patients with solid tumors utilizing our proprietary ex vivo genetic and epigenetic T‑cell reprogramming technologies.

Our investigational therapies use the patient’s own cells as the starting point to generate highly tumor-reactive, longer-lasting functional T cells with enhanced ability to defeat solid tumors.

Our innovative reprogramming technologies address what we believe are the primary barriers that limit consistent and long-lasting responses to T‑cell therapy in solid tumors:

T‑cell exhaustion and lack of durable stemness.

Our technologies are designed to generate T cells with the ability to persist and self‑renew while driving durable tumor cytotoxicity, even in the setting of an immunosuppressive tumor microenvironment.

The goal is for our technologies to provide patients with T cells that are potent and long-lasting enough to achieve durable antitumor responses.

Furthermore, our technologies can be applied in a target agnostic manner to multiple T‑cell modalities, including chimeric antigen receptor (CAR), tumor-infiltrating lymphocytes (TIL) and T‑cell receptor (TCR) therapies.

We apply our technologies with the aim to develop T‑cell therapies with improved durable clinical outcomes.

Our growing pipeline of promising cell product candidates targets solid tumor indications with large unmet needs that are collectively responsible for approximately 180,000 deaths in the US annually.

Each of our programs provide opportunities to expand into additional indications beyond the patient populations we are initially targeting.

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Pipeline Programs and Operational Updates

Pipeline Programs

Phase 1 clinical development of two product candidates (LYL797, LYL132) has commenced and additional product candidates are in preclinical development (LYL845, LYL331).

LYL797 and LYL845 are wholly‑owned by Lyell, and LYL132 and LYL331 are being developed in collaboration with GSK.

LYL797 – CAR T-cell therapy targeting ROR1 + solid tumors, incorporating Gen-R and Epi-R

• Announced FDA clearance of the IND for LYL797, a chimeric antigen receptor (CAR) T-cell therapy for patients with solid tumors expressing receptor tyrosine kinase-like orphan receptor 1 (ROR1 + ).

• Screening initiated for the Phase 1 open label dose escalation and expansion trial with relapsed/refractory triple-negative breast cancer or non-small cell lung cancer who have failed at least two lines of therapy, initial data expected in 2023.

LYL132 – TCR therapy targeting NY-ESO-1 solid tumors, incorporating Epi-R

• Announced FDA clearance of the IND for LYL132, a T-cell receptor (TCR) therapy developed in collaboration with GSK for patients with solid tumors expressing New York esophageal squamous cell carcinoma 1 (NY-ESO-1).

LYL845 - TIL therapy designed to target multiple solid tumor indications, incorporating Epi-R

• On track to submit an IND in the second half of 2022 for LYL845, a tumor infiltrating lymphocyte (TIL) therapy.

• Initially targeting melanoma, with plans to expand into additional solid tumor indications.

LYL331 - TCR therapy targeting NY-ESO-1 solid tumors, incorporating Gen-R

• GSK has communicated to us that due to updated manufacturing timing, the IND for LYL331 is likely to be submitted in late 2022/early 2023.

• LYL331 is a TCR therapy developed in collaboration with GSK for patients with solid tumors expressing New York esophageal squamous cell carcinoma 1 (NY-ESO-1).

• LYL331 incorporates Gen-R and, along with LYL132, is under investigation as a potential next-generation enhancement to lete-cel.

Operational Updates

• Announced cGMP qualification of LyFE™, Lyell’s manufacturing facility designed to produce cell products at scale for upcoming clinical trials across its CAR, TIL and TCR products.

COVID-19 Update

The global COVID-19 pandemic continues to evolve rapidly, and we will continue to monitor it closely.

The extent of the impact of the COVID-19 pandemic on our business, operations and development timelines and plans remains uncertain and will depend on certain developments, including the duration and spread of the outbreak and its impact on our clinical trial plans, CROs, contract manufacturing organizations and other third parties with whom we do business, as well as its impact on regulatory authorities and our key scientific and management personnel.

While the implications of the COVID-19 pandemic on our operations remain uncertain, to date, we have not experienced delays in our discovery and development activities as a result of the COVID-19 pandemic.

However, there can be no assurance that we will be able to avoid materially adverse impacts from the evolving effects of the COVID-19 pandemic.

In this regard, site initiation and patient enrollment may be delayed due to prioritization of hospital resources toward the COVID-19 pandemic, which may delay enrollment in our current and planned clinical trials, and some patients may not be able to comply with clinical trial protocols if quarantines impede patient movement or interrupt healthcare services, and we may be unable to obtain blood samples for testing.

We are advancing four wholly-owned product candidates;

two product candidates, LYL797 and LYL845, are in Phase 1 clinical development and two additional product candidates, LYL119 and a TIL product candidate incorporating novel genetic and epigenetic reprogramming technologies, are in preclinical development.

LYL797 – A ROR1 CAR T-cell product candidate genetically reprogrammed using c-Jun and epigenetically reprogrammed using our proprietary Epi-R manufacturing protocol, designed for differentiated potency and durability

• Enrollment in the Phase 1 clinical trial of LYL797 is ongoing.

Initial clinical data from the Phase 1 trial of LYL797 are expected in the first half of 2024.

• Presented nonclinical data at the American Association of Cancer Research 2022 Annual Meeting characterizing LYL797 and demonstrating that our c-Jun overexpression and Epi-R reprogramming technologies can overcome barriers of T-cell exhaustion and lack of durable stemness in engineered T cells using a set of in vitro and in vivo models, including an aggressive syngeneic mouse tumor model and a xenograft lung cancer model.

• Presented nonclinical data demonstrating LYL797 showed improved expansion and anti-tumor activity and prolonged survival compared to conventional ROR1 CAR T cells in an established human ROR1-positive H1975 mouse xenograft model at the American Society of Gene and Cell Therapy Annual Meeting.

LYL119 – An innovative ROR1 CAR T-cell product designed for enhanced cytotoxicity

• LYL119 incorporates four of our stackable reprogramming technologies, including two novel technologies – a genetic knockout of NR4A3 and Stim-R.

These technologies, which are complementary to c-Jun and Epi-R, are designed to further improve the anti-tumor potency and durability of T-cells.

• An IND for LYL119 is expected to be submitted in the first half of 2024.

• Presented nonclinical data demonstrating that the combination of two genetic reprogramming technologies, NR4A3 gene knockout and c-Jun overexpression, enhances the functional activity of ROR1 CAR T cells as shown by higher levels of cytokine production, increased CAR T-cell persistence and reduced surface expression of inhibitory receptors after repetitive antigen stimulation, as well as significant improvement in tumor control in vivo at The Society for Immunotherapy of Cancer 2022 Annual Meeting (SITC 2022).

• Presented nonclinical data at SITC 2022 demonstrating that our proprietary Stim-R epigenetic reprogramming technology, which enables precise control and optimized delivery of activation molecules during T-cell production, generates potent CAR T-cell product candidates with increased cell proliferation and persistence, as well as improved tumor control in vivo .

LYL845 – A novel epigenetically reprogrammed TIL product candidate designed for differentiated potency and durability

• Announced clearance of the IND for LYL845 in October 2022;

enrollment in the Phase 1 clinical trial for LYL845 is ongoing.

Initial clinical data from the Phase 1 trial of LYL845 are expected in 2024.

• Presented nonclinical data at SITC 2022 demonstrating the ability of Lyell’s Epi-R technology to successfully expand TIL in both hot and cold tumors and to retain qualities linked with anti-tumor functionality and improved outcomes in previous TIL clinical trials.

These qualities present in our Epi-R TIL include a greater proportion of CD8+ T cells, enrichment for T cells with stem-like profiles, better metabolic fitness and preserved polyclonality compared to control TIL preparations.

• Presented bioinformatic analyses, including comprehensive analyses of transcriptomic profiles, polyclonality and prediction of tumor-reactive T cell clones in our LYL845 product candidate, at SITC 2022.

These analyses demonstrated that LYL845 expanded at clinical scale using Epi-R technology remained highly polyclonal and preserved approximately 94% of the predicted tumor reactive clones.

Further, the preserved predicted tumor reactive clones in LYL845 have increased stemness and reduced exhaustion‑associated genes compared to TIL products derived from the standard process.

Corporate and Operational Updates

• In December, Lynn Seely, M.D., a member of the company’s board since May 2021 and former President and CEO of Myovant Sciences, was named President and CEO.

Seely has extensive biopharmaceutical leadership experience with a track record of success building companies and developing new medicines in oncology and women’s health.

• In September, Rahsaan W.

Thompson was named Chief Legal Officer.

Thompson is a biopharmaceutical industry veteran with more than 20 years of experience with development stage and commercial companies.

• In January, Gary Lee, Ph.D.

was named Chief Scientific Officer.

Lee is a veteran biotech leader with more than a decade of experience heading translational cell and gene therapy programs.

Macroeconomic Environment

Our business and operations may be affected by worldwide economic conditions, which may continue to be impacted by global macroeconomic challenges such as the effects of the ongoing geopolitical conflicts in Ukraine, tensions in U.S.-China relations, the COVID-19 pandemic, uncertainty in the markets and inflationary trends.

Fiscal year 2022 was marked by significant market uncertainty, increasing inflationary pressures, supply constraints and ongoing effects from the COVID-19 pandemic.

These market dynamics may continue into 2023 and these and similar adverse market conditions may negatively impact our business.

In particular, as the global COVID-19 pandemic and its effects continue to evolve, the extent of the impact of the COVID-19 pandemic on our business, operations and development timelines and plans remains uncertain and will continue to depend on certain developments, including the duration and spread of the outbreak, other next-level effects and the impact on our CROs, contract manufacturing organizations, clinical sites and other third parties with whom we do business, as well as the impact on regulatory authorities and our key scientific and management personnel.

There can be no assurance that we will be able to avoid materially adverse impacts from the effects of the COVID-19 pandemic.

The effects of the COVID-19 pandemic may continue to negatively impact healthcare and hospital resources, including both front-line and administrative staff, which may delay enrollment in our current and planned clinical trials.

Some patients may not be able to comply with clinical trial protocols due to potential quarantines, lack of healthcare support or potential interruptions of healthcare services, and we may be unable to obtain blood samples for testing.

For example, limitations or modifications in surgery scheduling for oncology patients at collaborating institutions has limited and may continue to limit supply of patient tumor samples that we use in our research.

We have closely monitored the COVID-19 pandemic and have strived to follow recommended containment and mitigation measures, including the guidance from the Centers for Disease Control and Prevention (CDC) as well as the states of California and Washington and applicable counties.

For most of the pandemic, essential laboratory and support employees worked in our facilities to continue and progress experiments.

We implemented preventative measures at our facilities in order to minimize the risk of employee exposure to the virus, including the following requirements:

that each employee who entered a facility agreed to comply with social distancing, frequent hand washing and the requirement to wear masks.

We also increased cleaning of high touch areas, provided hand sanitizing stations and implemented an employee questionnaire to ensure employee health status and to provide for limited on-site tracing if needed.

Finally, commencing in early March 2020, we suspended all non-essential business travel and adopted a work from home policy in which work that can be done from home is encouraged and allowed to be done from home.

We expect to continue such measures for the near foreseeable future, though we may allow certain designated groups of employees to return to our facilities on an as-needed basis if we determine that we may do so while continuing to maintain a safe work environment.

We will continue to actively monitor the situation related to the COVID-19 pandemic and may take further actions that alter our operations, including those that may be required by federal, state or local authorities, or that we determine are in the best interests of our employees and other third parties with whom we do business.

Collaboration, License and Success Payment Agreements

For a detailed description of our collaboration, license and success payment agreements, see the section titled “Business—Collaboration, License and Success Payment Agreements” in Part I, Item 1 of this Annual Report on Form 10‑K and Notes 2 and 3 to our audited consolidated financial statements included in Part II, Item 8 of this Annual Report on Form 10-K.

For a further discussion of trends, uncertainties and other factors that could impact our operating results, see the section entitled “Risk Factors” in Part I, Item 1A of this Annual Report on Form 10-K.

License, Collaboration and Success Payment Agreements

For a detailed description of our license, collaboration and success payment agreements, see the section titled “ Business—License, Collaboration and Success Payment Agreements ” in Part I, Item 1 of this Annual Report on Form 10‑K and Notes 2 and 3 to our audited consolidated financial statements included in Part II, Item 8 of this Annual Report on Form 10-K.

Components of Results of Operations

We have no products approved for sale and have never generated any revenue from product sales.

To date, we have generated revenue primarily from the recognition of a portion of the upfront payment under the GSK Agreement that we entered into in May 2019.

As we continue to conduct research under the GSK Agreement, we will recognize revenue based upon our estimate of the progress made.

We have generated revenue primarily from the recognition of the upfront payment under the GSK Agreement, entered into in 2019 and amended in June 2020 and December 2021 with GSK.

GSK terminated the GSK Agreement effective December 2022 and we do not expect further revenue from the collaboration.

See Note 3, License, Collaboration and Success Payment Agreements , in the accompanying notes to our audited consolidated financial statements included in Part II, Item 8 of this Annual Report on Form 10-K for additional details regarding termination of the GSK Agreement.

In the future, we may generate additional revenue from other collaborations, strategic alliances, licensing agreements, product sales, or a combination of these.

Operating Expenses (Income)

Operating Expenses

Research and Development

To date, research and development expenses consist of costs incurred by us for the discovery and development of our technology platforms and product candidates, and includes costs incurred in connection with strategic collaborations, costs to license technology, personnel-related costs, including stock-based compensation expense, facility and technology related costs, research and laboratory expenses, as well as other expenses, which include consulting fees and other costs.

To date, research and development expenses consist of costs incurred by us for the discovery and development of our technology platforms and product candidates, and include costs incurred in connection with strategic collaborations, costs to license technology, personnel-related costs, including stock-based compensation expense, facility and technology related costs, research and laboratory expenses, as well as other expenses, which include consulting fees and other costs.

Upfront payments and milestones paid to third parties in connection with technology platforms that have not reached technological feasibility and do not have an alternative future use are expensed as incurred.

Research and development expenses also include non-cash expense related to the change in the esti mated fair value of the liabilities associated with our success payments granted to Fred Hutch and Stanford.

Research and development expenses also include non-cash expenses related to the change in the esti mated fair value of the liabilities associated with our success payments granted to Fred Hutch and Stanford .

See the subsection titled “Critical Accounting Policies and Estimates— Success Payments ” below.

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Research and development activities account for a significant portion of our operating expenses.

We anticipate that our research and development expenses will increase over the foreseeable future as we expand our research and development efforts including completing preclinical studies, commencing planned clinical trials, conducting and completing current and planned clinical trials, seeking regulatory approval of our product candidates, identifying new product candidates and incurring costs to acquire and license technology platforms.

A change in the outcome of any of these variables could mean a significant change in the costs and timing associated with the development of our product candidates.

Because we are early in our research and development efforts and just beginning clinical development of our product candidates, and the outcome of these efforts is uncertain, we cannot estimate the actual amounts necessary to successfully complete the preclinical development, clinical development and commercialization of product candidates or whether, or when, we may achieve profitability.

We anticipate that our research and development expenses will increase over the foreseeable future as we expand our research and development efforts including completing nonclinical studies, commencing planned clinical trials, conducting and completing current and planned clinical trials, seeking regulatory approval of our product candidates, identifying new product candidates and incurring costs to acquire and license technology platforms.

A change in the outcome of any of these variables could mean a significant change in the costs and timing associated with the development of our product

Because we are early in our research and development efforts and beginning clinical development of our product candidates, and the outcome of these efforts is uncertain, we cannot estimate the actual amounts necessary to successfully complete the nonclinical development, clinical development and commercialization of product candidates or whether, or when, we may achieve profitability.

Our research and development expenses may vary significantly based on factors such as:

• the number and scope of preclinical and IND-enabling studies;

• the number and scope of nonclinical and IND-enabling studies;

• per patient trial costs;

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We may never succeed in obtaining regulatory approval for any of our product candidates.

We may obtain unexpected results from our preclinical studies and future clinical trials.

We may obtain unexpected results from our nonclinical studies and clinical trials.

General and Administrative

General and administrative costs include personnel-related expenses, including stock-based compensation expense for personnel in executive, legal, finance and other administrative functions, legal costs, transaction costs related to collaboration and licensing agreements, as well as fees paid for accounting and tax services, consulting fees and facilities costs not otherwise included in research and development expenses.

Legal costs include those related to corporate and patent matters.

Legal costs include those related to corporate, dispute and patent matters.

We anticipate that our general and administrative expenses will increase over the foreseeable future to support our continued research and development activities, operations generally, future business development opportunities, consulting fees, as well as due to the increased costs of operating as a public company such as costs related to accounting, audit, legal, regulatory and tax-related services associated with maintaining compliance with exchange listing and SEC requirements, director and officer insurance costs and investor and public relations costs.

Other Operating Income, Net

Other operating income, net consists primarily of service and occupancy fees received associated with subleases as well as gains or losses on t he sales of property and equipment.

Other operating income, net consists primarily of service and occupancy fees received associated with subleases as well as losses on t he retirement of property and equipment.

Interest Income, Net

Interest income, net consists primarily of interest earned on our cash, cash equivalents and marketable securities balances.

Other (Expense) Income, Net

Other (expense) income, net consists primarily of changes in the fair value of an equity warrant investment held.

Other Income (Expense), Net

Other income (expense), net consists primarily of a gain to record the PACT Series D convertible preferred shares, in addition to changes in the fair value of an equity warrant investment held.

Impairment of Other Investments

Impairment of other investments consists of impairment of the PACT Series C-1 convertible preferred stock investment.

Deemed Dividends Upon Issuance or Repurchase of Convertible Preferred Stock

Deemed dividends upon issuance or repurchase of convertible preferred stock consists of the amount by which the fair value of the convertible preferred stock exceeded the cash proceeds from the sale and issuance of such convertible preferred stock or the amount by which the cash paid for the repurchase of convertible preferred stock exceeded the carrying value of such convertible preferred stock.

Impairment of other investments consists of a reduction in the value of certain other investments.

Deemed Dividends Upon Repurchase of Convertible Preferred Stock

Deemed dividends upon repurchase of convertible preferred stock consists of the amount by which the cash paid for the repurchase of convertible preferred stock exceeded the carrying value of such convertible preferred stock.

Upon the closing of our IPO, all our convertible preferred stock was converted into our common stock.

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Year Ended December 31,

2021 2020 2019 2021 vs 2020 2020 vs 2019

2022 2021 2020 2022 vs 2021

$ 84,683 $ 10,650 $ 7,756 $ 74,033 $ 2,894

Operating expenses (income):

Operating expenses:

Research and development

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7,053 1,165 5,939 5,888 (4,774)

Other (expense) income, net

Other income (expense), net

1,887 (161) 1,526 2,048 (1,687)

Impairment of other investments (5,000) (36,447) — 31,447 (36,447)

Total other (loss) income, net (35,443) 7,465 (27,288) (42,908) 34,753

Total other income (loss), net 3,940 (35,443) 7,465 39,383 (42,908)

(183,118) (250,219) (204,472) 67,101 (45,747)

Deemed dividends upon issuance or repurchase of convertible preferred stock

Deemed dividends upon repurchase of convertible preferred stock

— — (3,582) — 3,582

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$ (183,118) $ (250,219) $ (208,054) $ 67,101 $ (42,165)

Revenue was $10.7 million and $7.8 million for the years ended December 31, 2021 and 2020, respectively, primarily related to the recognized portion of the upfront license fee pursuant to the GSK Agreement.

The increase of $2.9 million was primarily due to progress in research and development activities under the GSK Agreement.

Reven ue was $84.7 million and $10.7 million for the years ended December 31, 2022 and 2021, respectively, primarily related to the recognized portion of the upfront license fee pursuant to the GSK Agreement.

The increase of $74.0 million was primarily related to $83.6 million in revenue adjustments driven by the mutual agreement with GSK to conclude certain research activities in June 2022 and GSK’s subsequent termination of the GSK Agreement, effective December 2022, both of which resulted in changes to the measure of proportional cumulative performance.

The revenue increase was offset by a decrease of $9.6 million due primarily to fewer research and development activities under the GSK Agreement for the year ended December 31, 2022 .

See Note 3, License, Collaboration and Success Payment Agreements in the accompanying notes to our audited consolidated financial statements included in Part II, Item 8, of this Annual Report on Form 10-K for additional information about the termination of the GSK Agreement.

Research and Development Expenses

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Year Ended December 31,

2021 2020 2019 2021 vs 2020 2020 vs 2019

2022 2021 2020 2022 vs 2021

$ 70,483 $ 60,499 $ 54,112 $ 9,984 $ 6,387

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Research and developm ent expenses were $159.2 million and $138.7 million for the years ended December 31, 2022 and 2021, respectively.

The decrease of $43.6 million was primarily due to:

• a decrease of $62.8 million in collaborations, research activities and outside services expenses due to the commitment agreement upfront payment to PACT of $63.6 million and a decrease of $7.5 million in acquired in-process research and development expense related to the asset acquisition of Immulus, Inc., both recorded in 2020.

These decreases were offset by a $4.8 million increase in costs associated with collaboration agreements and a $3.5 million increase related to professional services;

• a decrease of $1.6 million in success payment expenses associated with our Fred Hutch and Stanford success payment liabilities, primarily driven by the decrease in the per share fair value of our common stock;

• an increase of $14.5 million in facilities and technology costs, primarily related to increased infrastructure to support our expansion in research and development, manufacturing capabilities and associated headcount growth;

• an increase of $6.4 million in personnel-related expenses, which was primarily related to an increase in headcount to expand our research, development and manufacturing capabilities.

The increase of $20.5 million was primarily due to an increase of $13.1 million i n facilities and technology costs, primarily related to increased infrastructure to support our expansion in research and development, manufacturing capabilities and associated headcount g rowth;

an increase of $10.0 million i n personnel-related expenses, that wa s primarily related to an increase in headcount to expand our research, development and manufacturing capabilities;

an increase of $6.3 million in collaboration, research activities and outside services primarily driven by an increase of $5.1 million in research and laboratory costs principally due to clinical trials;

and an increase of $3.3 million in professional services offset by a reduction of $2.2 million in collaboration and license fees;

partially offset by a decrease of $8.8 million in success payment expenses associated with our Fred Hutch and Stanfo rd success payment liabilities, primarily driven by the decrease in the per share fair value of our common stock.

General and Administrative Expenses

General and administrative expenses were $89.1 million and $46.9 million for the years ended December 31, 2021 and 2020, respectively.

The increase of $42.2 million was primarily due to an increase of $28.6 million in stock-based compensation expense, primarily related to award modifications, accelerations and new awards granted, and $2.4 million increase in personnel-related expenses due to an increase in headcount to support our operations.

A dditionally, outside services and corporate expenses increased by $7.3 million due to certain litigation costs and an increase of $3.2 million in costs associated with operating as a public company.

General and administrative expenses w ere $117.3 million and $89.1 million for the years ended December 31, 2022 and 2021, respectively.

The increase of $28.3 million was primarily due to an increase of $18.3 million in stock-based compensation expense, primarily related to award modifications and new awards granted.

A dditionally, outside services increased by $5.1 million due primarily to higher legal expenses and corporate expenses increased $3.9 million primarily due to costs associated with operating as a public company.

Other Operating Income, Net

Other operating income, net was $4.8 million and $2.3 million for the years ended December 31, 2022 and 2021, respectively.

The decrease of $7.1 million was due primarily to two significant gains that occurred in 2020, a gain recorded on the sale of assets of $4.9 million and a gain recorded upon lease remeasurement of $2.9 million.

The increase of $2.4 million wa s due primarily to sublease income and operating fees related to our subleases.

Interest Income, Net

Interest income, net was $7.1 million and $1.2 million for the years ended December 31, 2022 and 2021, respectively.

The decrease of $4.8 million was due to lower interest rates earned on cash, cash equivalents and marketable securities balances.

Other (Expense) Income, Net

For the years ended December 31, 2021 and 2020, other (expense) income, net consisted primarily of the change in fair value of an equity warrant investment held.

The increase of $5.9 million was primarily driven by higher interest rates in 2022.

Other Income (Expense), Net

Other income (expense), net was $1.9 million and $(0.2) million for the years ended December 31, 2022 and 2021, respectively.

The increase of $2.0 million consisted primarily of a gain of $2.9 million to record the estimated fair value of PACT Series D convertible preferred shares acquired, offset by a decrease of $1.1 million in the fair value of an equity warrant investment held.

Impairment of Other Investments

For the year ended December 31, 2022, the $5.0 million impairment of other investments consisted of the full impairment of one of our other investments.

For the year ended December 31, 2021, the $36.4 million impairment of other investments consisted of the full impairment of our investment in PACT Series C-1 convertible preferred stock.

See Note 5, Other Investments , in the accompanying notes to our audited consolidated financial statements included in Part II, Item 8, of this Annual Report on Form 10-K for additional information.

Liquidity and Capital Resources

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Since our inception, we have funded our operations primarily through the sale and issuance of convertible preferred stock, the sale of common stock in connection with our IPO and business development activities.

As of December 31, 2021, we had $898.3 million in cash, cash equivalents and marketable securities.

As of December 31, 2022, we ha d $710.3 million in cas h, cash equivalents and marketable securities.

Since our inception, we have incurred significant operating losses.

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We had an accumulated deficit of $767.5 million as of December 31, 2022.

From June 29, 2018 (inception) through December 31, 2021, we raised an aggregate of $1,405.7 million in gross proceeds from the sales of our convertible preferred stock.

From June 29, 2018 (inception) through December 31, 2022, we raised an aggregate of $1,405.7 million in gross proceeds from the sales of our convertible preferred stock and the IPO.

On August 4, 2022, we entered into an Equity Distribution Agreement (the Equity Distribution Agreement) with Goldman Sachs & Co.

LLC (Goldman Sachs) and BofA Securities, Inc.

(BofA, and together with Goldman Sachs, the Agents) with respect to an at-the-market offering program.

In accordance with the terms of the Equity Distribution Agreement, we may offer and sell from time to time through the Agents shares of our common stock having an aggregate offering amount of up to $200.0 million (the Placement Shares).

Sales of the Placement Shares, if any, will be made at prevailing market prices on Nasdaq at the time of sale, or as otherwise agreed with the Agents, by any method permitted by law deemed to be an “at-the-market offering” as defined in Rule 415 of the Securities Act.

We will pay commissions to the Agents of up to 3.0% of the gross proceeds of the sale of the Placement Shares sold under the Equity Distribution Agreement and reimburse the Agents for certain expenses.

Neither us nor the Agents are obligated to sell any shares and to date, we have not made any sales under the Equity Distribution Agreement.

Future Funding Requirements

We expect to incur additional losses in the foreseeable future as we conduct and expand our research and development efforts, including conducting preclinical studies and clinical trials, developing new product candidates, establishing internal manufacturing capabilities and funding our operations generally.

We expect to incur additional losses in the foreseeable future as we conduct and expand our research and development efforts, including conducting nonclinical studies and clinical trials, developing new product candidates, establishing internal manufacturing capabilities and funding our operations generally.

Based on our current operating plan, we believe that our existing cash, cash equivalents and marketable securities will be sufficient to meet our working capital and capital expenditure needs into 2026.

However, we anticipate that we will need to raise additional capital in the future to fund our operations, including the commercialization of any approved product candidates.

However, we anticipate that we will need to raise additional capital in the future to fund our operations, including further development of our product candidates and the commercialization of any approved product candidates.

In addition, we regularly consider fund-raising opportunities and may decide, from time to time, to raise additional capital, including pursuant to the Equity Distribution Agreement, based on various factors, including market conditions and our plans of operation.

We are subject to the risks typically related to the development of new products, and we may encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business.

Our future capital requirements will depend on many factors, including:

• the scope, timing, progress, costs and results of discovery, preclinical development and clinical trials for our current and future product candidates;

• the scope, timing, progress, costs and results of discovery, nonclinical development and clinical trials for our current and future product candidates;

• the number of clinical trials required for regulatory approval of our current and future product candidates;

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• the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims;

• our ability to maintain existing, and establish new, collaborations, licenses, product acquisitions or other strategic transactions and the fulfillment of our financial obligations under any such agreements, including the timing and amount of any success payment, future contingent, milestone, royalty or other payments due under any such agreement;

• our ability to maintain existing, and establish new, collaborations, licenses, product acquisitions or other strategic transactions and the fulfillment of our financial obligations under any such agreements, including the timing and amount of any success payment, future contingent payments, milestone, royalty or other payments due under any such agreement;

• the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval;

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• the extent to which we acquire or invest in businesses, products and technology platforms.

Until such time as we complete preclinical and clinical development and receive regulatory approval of our product candidates and can generate significant revenue from product sales, if ever, we expect to finance our operations from the sale of additional equity or debt financings, or other capital which come in the form of strategic collaborations, licensing, or other arrangements.

Until such time as we complete nonclinical and clinical development and receive regulatory approval of our product candidates and can generate significant revenue from product sales, if ever, we expect to finance our operations from the sale of additional equity or debt financings, or other capital which come in the form of strategic collaborations, licensing, or other arrangements.

In the event that additional capital is required, we may not be able to raise it on terms acceptable to us, or at all.

If we raise additional funds through the issuance of equity or convertible debt securities, it may result in dilution to our existing stockholders.

If we raise additional funds through the issuance of equity or convertible debt securities, including pursuant to the Equity Distribution Agreement, it may result in dilution to our existing stockholders.

Debt financing or preferred equity financing, if available, may result in increased fixed payment obligations, and the existence of securities with rights that may be senior to those of our common stock.

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If we raise funds through strategic collaboration, licensing, or other arrangements, we may relinquish significant rights or grant licenses on terms that are not favorable to us.

Our ability to raise additional funds may be adversely impacted by potential worsening global economic conditions and the recent disruptions to, and volatility in, the credit and financial markets in the United States and worldwide resulting from the ongoing COVID-19 pandemic and otherwise.

If we are unable to raise additional capital when desired, our business, results of operations and financial condition would be adversely affected.

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We continually evaluate our liquidity and capital resources to ensure that we can adequately and efficiently finance our operations.

As of December 31, 2021 , our material cash requirements consisted primarily of paying salaries and benefits, administering clinical trials, providing the technology and facilities necessary to support our operations, operating lease obligations, potential success payments to Fred Hutch and Stanford and other payments related to our collaborative agreements.

See Note 3, Collaboration, License and Success Payment Agreements , and Note 9, Leases , in the accompanying notes to our audited consolidated financial statements included in Part II, Item 8, of this Annual Report on Form 10-K for additional information.

As of December 31, 2022 , our material cash requirements consisted primarily of paying salaries and benefits, administering clinical trials, conducting research, improving our manufacturing capabilities, providing the technology and facilities necessary to support our operations, funding operating lease obligations and other payments related to our collaborative agreements.

See Note 3, License, Collaboration and Success Payment Agreements , and Note 9, Leases , in the accompanying notes to our audited consolidated financial statements included in Part II, Item 8, of this Annual Report on Form 10-K for additional information.

The following table summarizes our cash flows for the periods indicated (in thousands):

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2022 2021 2020

Net cash provided by (used in):

Net cash (used in) provided by:

Operating activities

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10,635 401,244 476,790

Net increase (decrease) in cash, cash equivalents and restricted cash

Net (decrease) increase in cash, cash equivalents and restricted cash

$ (170,460) $ 153,422 $ 42,400

Operating Activities

During the year ended December 31, 2021, net cash used in operating activities was $126.2 million, consisting primarily of our net loss of $250.2 million, partially offset by certain non-cash items such as stock-based compensation expense of $62.2 million, impairment of other investments of $36.4 million, depreciat ion and amortization expense of $13.6 million and the change in fair value of success payment liabilities of $3.7 million.

Additionally, net operating assets and liabilities increased $4.0 million, which included an increase in operating lease liabilities due to tenant improvement allowances received of $13.3 million offset by the recognition of $10.5 million of revenue previously recorded in deferred revenue.

During the year ended December 31, 2022, net cash used in operating activities wa s $169.6 million, primarily reflecting our net loss of $183.1 million, a decrease of $82.0 million in net operating assets and liabilities primarily driven by a $84.7 million decrease in deferred revenue due to non-cash revenue recognized and a $2.0 million decrease in prepaid expenses, other current assets and other assets, offset by a $4.9 million increase in operating lease liabilities due primarily to tenant improvement allowances received.

These decreases were partially offset by $95.6 million of non-cash expenses primarily related to stock-based compensation of $81.9 million, depreciation and amortization of $18.0 million and impairment of other investments of $5.0 million.

Additionally, we recognized decreases for the $5.1 million change in the fair value of success payment liabilities and $2.9 million for the non-cash adjustment of the gain on other investments.

During the ye ar ended December 31, 2021, net cash used in operating activities was $126.2 million , consisting primarily of our net loss of $250.2 million , partially offset by certain non-cash items such as stock-based compensation expense of $62.2 million , impairment of other investments of $36.4 million, depreciation and amortization expense of $13.6 million and the change in fair value of success payment liabilities of $3.7 million .

Additionally, net operating assets

and liabilities increased $4.0 million , which included an increase in operating lease liabilities due to tenant improvement allowances received of $13.3 million offset by the recognition of $10.5 million of revenue previously recorded as deferred revenue.

Investing Activ ities

During the year ended December 31, 2022, cash used in investing activities was $11.5 million, consisting of purchases of property and equipment of $24.3 million offset by net maturities, sales and purchases of marketable securities of $12.7 million.

During the year ended December 31, 2021, cash used in investing activities was $121.6 million , consisting of net purchases of marketable securities of $56.1 million and capital expenditures of $65.5 million .

Financing Activities

During the year ended December 31, 2022, cash provided by financing activities was $10.6 million, consisting of $9.6 million in proceeds from the exercise of stock options and $1.5 million in proceeds from the employee stock purchase plan, partially offset by $0.5 million in taxes paid related to the net share settlement of equity awards.

During the year ended December 31, 2021, cash provided by financing activities was $401.2 million, consisting of $391.8 million in net proceeds from the sale of our common stock in our IPO and $9.4 million in proceeds from the exercise of stock options.

Critical Accounting Policies and Estimates

Our audited consolidated financial statements are prepared in accordance with GAAP.

Critical Accounting Policies and Significant Judgments and Estimates

Our audited consolidated financial statements are prepared in accordance with U.S.

The preparation of these consolidated financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the audited consolidated financial statements, as well as the reported revenue and expenses incurred during the reporting periods.

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We are required to make success payments to Fred Hutch and Stanford based on increases in the per share market value of our common stock, payable in cash or cash equivalents or, at our discretion, publicly tradeable shares of our common stock.

The success payments are accounted for under ASC 718, Compensation – Stock Compensation , and are initially recorded at fair value with a corresponding charge to research and development expense.

The liabilities are marked to market at each balance sheet date with all changes in value recognized in research and development expense in the consolidated statement of operations.

Once their service periods are complete, the success payments will be accounted for under ASC 815, Derivatives and Hedging , and fair value changes will be recorded in other (expense) income, net.

The success payments are accounted for under Accounting Standards Codification (ASC) 718, Compensation – Stock Compensation , and are initially recorded at fair value with a corresponding charge to research and development expense.

The liabilities are marked to market at each balance sheet date with all changes in value recognized in research and development expense in the Consolidated Statements of Operations and Comprehensive Loss.

Once their service periods are complete , the success payments will be accounted for under ASC 815, Derivatives and Hedging , and fair value changes will be recorded in other income (expense), net.

We will continue to adjust the liabilities for changes in fair value until the earlier of the achievement or expiration of the success payment obligation.

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Stock-based Compensation

Stock-based compensation cost is recognized for restricted stock awards (“RSAs”), restricted stock units (“RSUs”), employee stock purchases related to the Employee Stock Purchase Plan and stock options.

Stock-based compensation cost is measured at the grant date based on the fair value of the award.

The fair value of stock-based awards is recognized as an expense on a straight-line basis over the requisite service period, with forfeitures recognized as they occur.

We use the Black-Scholes model to determine the fair value of our options.

The Black-Scholes option pricing model requires the use of assumptions, including stock price volatility, the expected life of stock options, risk-free interest rate and the fair value of the underlying common stock on the date of grant.

Our restricted stock awards and restricted stock units are valued based on the fair market value of the award on the grant date.

Prior to the closing of our IPO, the fair value of the common stock underlying our stock-based awards was estimated on each grant date by our board of directors using significant judgment to estimate the fair value of our common stock, including considering our stage of development;

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and the lack of marketability of our common stock.

The fair value of stock-based awards is recognized as an expense on a straight-line basis over the requisite service period, with forfeitures recognized as they occur.

We use the Black-Scholes model to determine the fair value of our options.

Our restricted stock awards are valued based on the fair market value of the award on the grant date.

Valuation of Other Investments

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Under the measurement alternative, the carrying value is measured at cost, less any impairment, plus or minus changes resulting from observable price changes in orderly transactions for the identical or a similar investment of the same issuer.

Determining whether an observed transaction is similar to a security within our portfolio requires judgment based on the rights and obligations of the securities.

Recording upward and downward adjustments to the carrying value of our equity securities as a result of observable price changes requires quantitative assessments of the fair value of our securities using various valuation methodologies and involves the use of estimates.

Non-marketable equity securities are also subject to periodic impairment reviews.

Determining whether an observed transaction is similar to a security within our portfolio requires judgment based on the rights and obligations of the investments.

Recording upward and downward adjustments to the carrying value of our equity investments as a result of observable price changes requires quantitative assessments of the fair value of our investments using various valuation methodologies and involves the use of estimates.

We determine at the inception of each arrangement whether an investment or other interest is considered a variable interest entity (VIE).

If the investment or other interest is determined to be a VIE, we evaluate whether we are considered the primary beneficiary.

The primary beneficiary of a VIE is the party that meets both of the following criteria:

(i) has the power to direct the activities that most significantly impact the VIE’s economic performance;

and (ii) has the obligation to absorb losses or the right to receive benefits from the VIE.

For any investments in VIEs in which we are considered the primary beneficiary, the assets, liabilities and results of operations of the VIE would be included in our consolidated financial statements.

As of December 31, 2022 and 2021, there were no VIEs for which we were the primary beneficiary.

Non-marketable equity investments are also subject to periodic impairment reviews.

Our quarterly impairment analysis considers both qualitative and quantitative factors that may have a significant effect on the investment’s fair value.

Qualitative factors considered include the companies’ financial and liquidity position, access to capital resources and the time since the last adjustment to fair value, among others.

When indicators of impairment exist, we prepare quantitative assessments of the fair value of our equity investments using both the market and income approaches that require judgment and the use of estimates, including discount rates, investee revenues and costs, and comparable market data of private and public companies, among others.

When our assessment indicates that an impairment exists, we write down the investment to its fair value.

We performed a qualitative assessment of potential indicators of impairment for 2022 and determined that indicators existed for one of our other investments with a carrying amount of $5.0 million.

While there was no single event or factor, we considered the underlying company’s operating cash flow requirements over the next year and liquid asset balances to fund those requirements and the uncertainty regarding the underlying company’s ability to raise funds as indicators of impairment.

Due to these indicators, we assessed the valuation of the investment and determined the fair value to be negligible and the impairment to be other-than-temporary in nature.

As a result, we recorded a $5.0 million impairment expense for the investment for the year ended December 31, 2022, which was recorded within impairment of other investments on the Consolidated Statement of Operations and Comprehensive Loss and as a reduction of the other investments on the Consolidated Balance Sheet.

In connection with the preparation of our financial statements for 2021, we performed a qualitative assessment of potential indicators of impairment and determined that indicators existed for our $36.4 million investment in PACT Series C-1 convertible preferred stock.

While there was no single event or factor, we considered PACT’s operating cash flow requirements over the next year and liquid asset balances to fund those requirements and their inability to raise funds as indicators of impairment.

Due to these indicators, we assessed the valuation of our investment in PACT as of December 31, 2021 and determined the fair value to be negligible and the impairment to be other-than-temporary in nature.

Due to these indicators, we assessed the valuation of our investment in PACT as of

December 31, 2021 and determined the fair value to be negligible and the impairment to be other-than-temporary in nature.

As a result, we recorded a $36.4 million impairment of our PACT investment in the fourth quarter of 2021.

The impairment charge was recorded within impairment of other investments on the Consolidated Statement of Operations and Comprehensive Loss and as a reduction to the investment balance within other investments on the Consolidated Balance Sheet.

The impairment charge was recorded within impairment of other investments on the Consolidated Statement of Operations and Comprehensive Loss and as a reduction of the other investments on the Consolidated Balance Sheet.

Recently Adopted and Recent Accounting Pronouncements

See Note 2, Basis of Presentation and Significant Accounting Policies, in the accompanying notes to our audited consolidated financial statements included in Part II, Item 8 of this Annual Report on Form 10-K for information about recent accounting pronouncements, the timing of their adoption and our assessment, to the extent we have made one yet, of their potential impact on our financial condition or results of operations.

JOBS Act Accounting Election

We are an “emerging growth company,” as defined in the JOBS Act.

For so long as we remain an emerging growth company, we are permitted and intend to rely on certain exemptions from various public company reporting requirements, including not being required to have our internal control over financial reporting audited by our independent registered public accounting firm pursuant to Section 404, reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statement, and exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and any golden parachute payments not previously approved.

In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards.

This allows an emerging growth company to delay the adoption of certain accounting standards until those standards would otherwise apply to private companies.

We have elected to use this extended transition period to enable us to comply with new or revised accounting standards that have different effective dates for public and private companies until the earlier of the date we (i) are no longer an emerging growth company or (ii) affirmatively and irrevocably opt out of the extended transition period provided in the JOBS Act.

As a result, our consolidated financial statements may not be comparable to companies that comply with new or revised accounting pronouncements as of public company effective dates.

We also intend to rely on other exemptions provided by the JOBS Act, including without limitation, not being required to comply with the auditor attestation requirements of Section 404.

We will remain an emerging growth company until the earliest of (i) the last day of the fiscal year following the fifth anniversary of the consummation of our initial public offering, (ii) the last day of the fiscal year in which we have total annual gross revenue of at least $1.07 billion, (iii) the last day of the fiscal year in which we are deemed to be a “large accelerated filer” as defined in Rule 12b-2 under the Exchange Act, or (iv) the date on which we have issued more than $1.0 billion in non-convertible debt securities during the prior three-year period.

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-K

Item 7. Management’s Discussion and Analysis