Lyell Immunopharma Inc
For the period ended Sep 30, 2024. Filed Nov 7, 2024.
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Sep 30, 2024 · Filed Nov 7, 2024
LYEL$14.86-0.9%Stored close · as of Nov 6, 2026
What changed in Management’s Discussion and Analysis?
Read the current filingPrevious report: 10-Q
Period ended 2024-06-30; filed 2024-08-07.
0001628280-24-035617
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsCurrent report: 10-Q
Period ended 2024-09-30; filed 2024-11-07.
0001628280-24-046285
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsThe baseline is this issuer’s latest earlier reporting period of the same form that was filed before the current report. A previous 10-Q is a different quarter, not a year-over-year comparison. Amendments are excluded.
Compared 142 previous paragraphs and 143 current paragraphs.
86 unchanged; 26 reworded; 31 added; 29 removed; 1 previous and 0 current paragraphs rearranged.
Tables are not compared: 3 previous and 3 current tables excluded. Dates, whitespace, punctuation and numbering changes are ignored; changes to financial figures remain significant.
A changed paragraph is not evidence that risk increased or decreased. An unchanged paragraph does not establish that risk stayed the same.
Added paragraphs (31)
Current report
We recently acquired ImmPACT Bio USA Inc. (ImmPACT), a privately-owned clinical stage biotechnology company developing next-generation CAR T-cell product candidates including a dual-targeting CD19/CD20 CAR T‑cell product candidate currently in Phase 1 clinical development for the treatment of aggressive B-cell non-Hodgkin lymphoma. In conjunction with this acquisition, we prioritized our pipeline to focus resources on our most differentiated next generation CAR T‑cell product candidates, including IMPT-314 for patients with aggressive B-cell lymphoma and
Current report
LYL119. LYL119, our next-generation ROR1‑targeted CAR T‑cell product candidate, has received FDA clearance of its Investigational New Drug (IND) application and is entering a Phase 1 dose-escalation, dose-expansion clinical trial, initially in patients with platinum-resistant ovarian cancer or relapsed/refractory endometrial cancer. We do not have any products approved for sale.
Current report
IMPT-314 - A next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of the response as compared to the approved CD19‑targeted CAR therapies for the treatment of large B-cell lymphoma.
Current report
IMPT-314 is an autologous dual-targeting CD19/CD20 CAR T-cell therapy designed to kill B‑cells expressing CD19 and/or CD20 antigens for the treatment of patients with aggressive B-cell malignancies. We acquired this product candidate through our acquisition of ImmPACT in October 2024.
Current report
A dual-targeting, or bispecific, CAR recognizes two targets. IMPT-314 is rationally designed with an ‘OR’ logic gate to target B cells that express either CD19, CD20 or both (Figure 1). This differentiates IMPT-314 from cell therapies and other therapeutic modalities that singularly target only CD19 or only CD20. Preclinical data demonstrated that this optimized tandem CAR design is capable of killing target cells that express CD19 only, CD20 only or both antigens, thus it has the potential to achieve a higher percentage of complete responses than a single targeting agent, particularly in those patients with lymphoma who may have a lower or heterogeneous CD19 antigen density.
Current report
Additionally, IMPT-314 is manufactured to produce a CAR T-cell product with higher proportions of naïve and central memory T cells through a proprietary process that enriches for CD62L-expressing cells. This manufacturing process is designed to generate CAR T cells with enhanced antitumor activity, that we believe could result in both increased complete response rates and more durable responses. Naïve T cells are mature T lymphocytes that have differentiated in the bone marrow and undergone central tolerance selection in the thymus, but have not interacted with their antigen. CAR T cells generated from these less differentiated T cells are known to have better engraftment, improved persistence, reduced exhaustion and lower cytokine production compared to CAR T cells generated from traditional processes. The enrichment of CD62L-positive naïve T cells does not increase the manufacturing time which is similar to that of the approved CD19 CAR T-cell therapies. Data from the ZUMA-7 pivotal trial of axicabtagene ciloleucel in patients with relapsed/refractory large B-cell lymphoma demonstrated an improved overall survival in those patients with a higher median percentage of T cells in the product with a naïve/stem memory phenotype (Westin JR, NEJM, 2023).
Current report
Figure 1: IMPT-314 contains separate, tandem single-chain variable fragment (scFV) antibody domains designed to target both CD19 and CD20 and is manufactured using a CAR that contains the 4-1BB costimulatory domain and a process to enrich for CD62-positive naïve and central memory T cells.
Current report
Non-Hodgkin lymphoma (NHL) is a common blood cancer in the United States and worldwide. Annually, it is estimated that approximately 81,000 people in the United States and 545,000 worldwide will be diagnosed with NHL. B‑cell lymphoma is the most common type of non-Hodgkin lymphoma, comprising approximately 85% of all lymphomas in the United States. While the first generation of CD19 CAR T-cell therapies delivered a major advance in treatment for patients with B-cell lymphoma, there remains a need for therapies that deliver more complete and durable responses. More than 40% of patients treated with a CD19 CAR T-cell therapy are not disease-free after treatment and 30% of patients do not respond at all. Of patients treated with an approved CD19 CAR T-cell therapy, approximately 50% of patients progress or relapse within six months. The overall survival at one year for patients treated with a CD19 CAR is only 50% to 60%.
Current report
ImmPACT licensed its dual-targeting CD19/CD20 CAR T-cell product candidate from the University of California Los Angeles (UCLA). Interim Phase 1 data in 13 patients with relapsed/refractory aggressive non-Hodgkin lymphoma treated in a UCLA‑sponsored clinical trial were presented at the 2024 American Association for Cancer Research (AACR) Special Conference in Cancer Research: Tumor Immunology and Immunotherapy (Figure 2). CAR T-cell naïve patients with relapsed/refractory diffuse large B-cell lymphoma or primary mediastinal B‑cell lymphoma after at least two lines of therapy or mantle cell lymphoma, follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma after at least three lines of therapy were evaluated. Autologous T cells were obtained and enriched for CD14-/CD25-/CD62L+ naïve or memory T cells. Two doses were to be evaluated including 50 and 200 million cells. Three patients received cell doses below 50 million cells due to manufacturing issues. Twelve out of 13 patients achieved a complete or partial response (92% objective response rate), with ten achieving a confirmed complete response (77% complete response rate). The median progression-free survival was 50.1 months, and median overall survival was not reached with a median follow‑up of 32 months (range: 5.7 – not estimable). A favorable safety profile was observed with no case of cytokine release syndrome (CRS) above Grade 1 and no reported cases of immune effector cell‑associated neurotoxicity syndrome (ICANS).
Current report
Figure 2: Interim Phase 1 data in 13 patients with relapsed/refractory aggressive non-Hodgkin lymphoma treated with UCLA-314 in a UCLA-sponsored clinical trial were presented at the 2024 AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy.
Current report
ImmPACT initiated a Phase 1-2 clinical trial of this dual-targeting CD19/CD20 CAR T-cell product candidate, IMPT-314, in 2023, and we are now advancing this trial. It is a multi-center, open-label dose-escalation and dose-expansion clinical trial designed to evaluate the safety and clinical benefit of IMPT-314 and to determine a recommended Phase 2 dose in patients with relapsed/refractory aggressive B-cell lymphoma. IMPT-314 has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of relapsed/refractory aggressive B-cell lymphoma.
Current report
•Initial data from the ongoing multi-center Phase 1-2 trial of IMPT-314 will be presented at the American Society of Hematology (ASH) Annual Meeting in December 2024.
Current report
•We expect to initiate a pivotal trial in patients with relapsed/refractory large B-cell lymphoma in the 3rd line setting who have not yet been exposed to CAR T-cell therapy in 2025.
Current report
LYL119 builds on what we learned from the preclinical and clinical development of LYL797, our first-generation ROR1-targeted CAR T‑cell product candidate that demonstrated dose-dependent clinical activity in the Phase 1 trial of patients with TNBC. LYL797 was enhanced with c-Jun overexpression and manufactured with our Epi-R protocol. A key pillar of our strategy is to continually innovate to develop and advance novel, breakthrough technologies that address key barriers to effective cell therapy for solid tumors and LYL119, our next-generation ROR1-targeted CAR T‑cell product candidate incorporates four technologies designed to further enhance the anti-exhaustion functionality and stem-like qualities of T cells. These technologies include c-Jun overexpression, NR4A3 knockout by gene editing, and manufacturing using our Epi-R protocol and Stim-R novel T-cell activation technology.
Current report
The enhanced anti-exhaustion technology incorporated into LYL119 has the potential to achieve improved efficacy at lower cell doses with an acceptable safety profile. In a preclinical mouse model of non-small cell lung cancer, LYL119 demonstrated greater antitumor potency and complete tumor control at a very low cell dose of only 100,000 cells, as well as significantly enhanced sustained tumor cell killing in a repetitive cancer cell killing assay in vitro as compared to LYL797 (Figures 3 and 4). The lower doses used with LYL119 also resulted in much more gradual cell expansion as demonstrated in Figure 5 with a logarithmic scale on the y-axis.
Current report
Figure 3: LYL119 demonstrated more potent anti-tumor activity in vivo in a NSCLC (H1975) xenograft model, with significantly improved elimination of tumors at the lower 0.1 x 106 CAR T-cell dose.
Current report
Figure 4: LYL119 demonstrates superior tumor cell killing following serial antigen restimulation.
Current report
Figure 5: More gradual cell in vivo expansion at lower doses of LYL119 suggests greater tolerability.
Current report
•Presenting a poster at the Society for Immunotherapy of Cancer (SITC) Annual Meeting titled “Multiomic profiling of LYL119: A Reprogrammed ROR1 CAR T Product Generates T cells with Reduced Exhaustion and Enhanced Memory Characteristics Associated with Increased AP-1 and Reduced NR4A Bindings.” In a validated preclinical xenograft model of NSCLC, LYL119 achieved complete tumor control and prolonged survival even at very low doses compared to LYL797, Lyell’s first generation ROR1-targeted CAR T‑cell product candidate. The study presented potential molecular mechanisms underlying the functional reduction of T-cell exhaustion and enhancement of memory‑related characteristics of LYL119 CAR T cells after antigen encounter in vitro and in vivo.
Current report
Additional Pipeline and Business Updates
Current report
In connection with the acquisition of ImmPACT, we acquired worldwide rights to ImmPACT’s pipeline, including the next-generation bispecific CD19/CD20 autologous CAR T-cell therapy (IMPT-314), currently in clinical development for B-cell lymphoma and autoimmune diseases, and an activating TGF-beta Claudin 18.2 CAR T-cell candidate, which is in preclinical development. We have prioritized our pipeline to focus on the development of IMPT-314 for patients with B-cell lymphoma and LYL119 for patients with solid tumors and have discontinued development of LYL797, our first-generation ROR1-targeted CAR T-cell product candidate.
Current report
While LYL797 achieved enhanced tumor cell killing over historical control clinical data, we subsequently discontinued development of this first-generation product candidate on October 31, 2024 due to continued events of pneumonitis despite dexamethasone prophylaxis, resulting in a narrow therapeutic window. We have prioritized our resources on the development of the next-generation product candidate, LYL119, which we believe has the potential for a broader therapeutic window as described above.
Current report
We have also discontinued, LYL845, our TIL clinical program because it did not achieve our criteria for differentiation from the approved TIL product, as well as our next-generation TIL and rejuvenation programs that were in preclinical development.
Current report
Acquisition of ImmPACT
Current report
Pursuant to the Agreement and Plan of Merger (the Merger Agreement) by and among us, ImmPACT, Inspire Merger Sub Inc., a Delaware corporation and our indirect, wholly-owned subsidiary, and WT Representative LLC, a Delaware limited liability company, solely in its capacity as the representative, agent and attorney-in-fact of ImmPACT securityholders, dated October 24, 2024, we acquired all of the outstanding equity interests of ImmPACT in exchange for an upfront payment of $30.0 million in cash (as adjusted by approximately $12.0 million for ImmPACT’s existing cash balance) and the issuance of 37.5 million shares of our common stock at closing. Contingent consideration payable following the closing includes (a) additional equity consideration of 12.5 million shares of our common stock upon the achievement of the earlier to occur of (i) the demonstration of certain clinical milestones or (ii) the receipt of certain regulatory approvals and (b) a low single‑digit royalty on future net sales of IMPT-314 in the United States.
Current report
As a result of the acquisition of ImmPACT, we assumed its rights and obligations under its license agreement with the Regents of the University of California, acting through The Technology Development Group of UCLA, dated February 18, 2021 (the UCLA License Agreement). Pursuant to the UCLA License Agreement, we are obligated to pay a nominal, tiered annual license maintenance fee each year of the term of the UCLA License Agreement until we make the first commercial sale of a licensed product and, upon the achievement of specified development, regulatory and commercial milestones, we are obligated to pay UCLA one-time milestone payments of up to an aggregate amount in the mid-single digit millions for each commercialized licensed product. In addition, we are obligated to pay UCLA a tiered royalty on worldwide annual net sales of any commercialized licensed products in the low- to mid-single digits percentage, subject to specified and capped reductions and a tiered minimum annual royalty payment of between a low-five figure and a low-six figure amount.
Current report
Three and Nine Months Ended September 30, 2024 and 2023
Current report
Other operating income, net was $0.7 million and $0.3 million for the three months ended September 30, 2024 and 2023, respectively, and $2.8 million and $2.1 million for the nine months ended September 30, 2024 and 2023, respectively.
Current report
•any future acquisitions, strategic investments, partnerships or alliances and the related financial terms and obligations, including liabilities assumed in connection with our acquisition of ImmPACT;
Current report
Subsequent to September 30, 2024, we entered into the Merger Agreement with ImmPACT pursuant to which we acquired all of the outstanding equity interests of ImmPACT in exchange for an upfront payment of $30.0 million in cash (as adjusted by approximately $12.0 million for ImmPACT’s existing cash balance) and the issuance of 37.5 million shares of our common stock at closing and agreeing to issue an additional 12.5 million shares of our common stock upon the achievement of certain clinical or regulatory milestones. Pursuant to the Merger Agreement, we have also agreed to make cash royalty payments to the pre-closing stockholders of ImmPACT based on a low single-digit royalty on future net sales of IMPT-314 in the United States.
Current report
In addition, as a result of the Merger, we assumed ImmPACT’s rights and obligations under the UCLA License Agreement, pursuant to which we are obligated to pay a nominal, tiered annual license maintenance fee each year of the term of the UCLA License Agreement until we make the first commercial sale of a licensed product and, upon the achievement of specified development, regulatory and commercial milestones, we are obligated to pay UCLA one‑time milestone payments of up to an aggregate amount in the mid-single digit millions for each commercialized licensed product. In addition, we are obligated to pay UCLA a tiered royalty on worldwide annual net sales of any commercialized licensed products in the low- to mid-single digits, subject to specified and capped reductions and a tiered minimum annual royalty payment of between a low-five figure and a low-six figure amount.
Removed paragraphs (29)
Previous report
We are advancing four wholly-owned product candidates. Two product candidates, LYL797 and LYL845, are in Phase 1 clinical development, and an additional product candidate, LYL119, is entering Phase 1 clinical development. A second-generation TIL product candidate is in preclinical development. Research stage programs include our proprietary T‑cell rejuvenation technology and other undisclosed T‑cell enhancing technologies.
Previous report
LYL797 - A ROR1 CAR T-cell product candidate enhanced with anti-exhaustion technology designed for improved tumor infiltration and tumor cell killing
Previous report
Significant subsets of patients with common cancers express ROR1. We initiated development of LYL797 for the treatment of ROR1-positive TNBC and NSCLC, two of the highest ROR1‑expressing solid tumor indications. Results from our own ROR1 screening program are consistent with what is reported in the literature. Using our immunohistochemistry assay in the screening for our Phase 1 trial, as of June 2024, we have found that approximately 50% of patients with TNBC and approximately 35% of patients with NSCLC have tumors that express ROR1.
Previous report
Our hypothesis that T-cell exhaustion is a key barrier in the treatment of solid tumors is informed by a clinical study previously conducted at the Fred Hutchinson Cancer Center. In this study, autologous ROR1-targeted CAR T cells infused into patients with CLL underwent rapid expansion and retained T-cell effector function, leading to tumor cell clearance and clinical responses. However, when CAR T cells generated with the same method were infused into patients with solid tumors such as TNBC or NSCLC, these T cells often failed to expand adequately, rapidly upregulated cell surface markers of T-cell exhaustion and adopted a dysfunctional state.
Previous report
We also plan to submit an investigational new drug (IND) application to initiate a second Phase 1 clinical trial of LYL797 in relapsed/refractory multiple myeloma and CLL, where it is estimated in the literature that 60% and 95% of patients’ malignancies, respectively, express ROR1. While recent advances in the treatment of multiple myeloma, including CAR T-cell therapy, have improved the survival outcomes in patients, the disease is not curable, and the vast majority of patients with multiple myeloma eventually relapse or become resistant to treatment. Thus, new treatments with different targets and modalities are needed. In the United States, it is estimated that approximately 36,000 people will be newly diagnosed with multiple myeloma in 2024. CLL is a less common hematologic malignancy, with approximately 21,000 new cases in the United States annually. Although current treatments are effective in achieving remission, CLL remains incurable and similar to multiple myeloma, CLL is likely to relapse and require further line(s) of therapy.
Previous report
We recently reported initial clinical and translational data from our ongoing Phase 1 trial:
Previous report
•Enrollment in the Phase 1 clinical trial of LYL797 is ongoing. The study was initiated in patients with relapsed/refractory TNBC or NSCLC and expanded to include patients with platinum-resistant ovarian or endometrial cancers.
Previous report
•The Phase 1 clinical trial is designed as an open-label, dose-escalation and -expansion trial in patients with relapsed/refractory TNBC or NSCLC and has been expanded to include patients with platinum-resistant ovarian or endometrial cancer. All patients enrolled have tumor specimens positive for ROR1 protein expression by immunohistochemistry. The expansion phase of the trial will enroll at least 15 patients with at least two tumor types.
Previous report
•Initial data from the Phase 1 clinical trial of LYL797 were reported in June 2024:
Previous report
◦The initial dataset of 20 treated patients included 16 patients with TNBC and four patients with NSCLC. All patients enrolled had relapsed/refractory metastatic disease with an average of six lines of prior therapies. Four dose levels, including two interim dose levels, have been explored to date: 50 x 106 cells, 100 x 106 cells, 150 x 106 cells and 300 x 106 cells. The efficacy evaluable subset included 16 patients, and the safety evaluable subset included 18 patients. The manufacturing success rate was 100%.
Previous report
◦Of the five patients with TNBC treated with LYL797 at the 150 x 106 cell dose level, the highest dose level cleared when the data were reported, two patients had confirmed partial responses to Day 90, resulting in an objective response rate (ORR) of 40% (Figure 1). The clinical benefit rate (CBR), defined as a best response of stable disease, partial response or complete response, was dose-dependent with a 60% CBR at the 150 x 106 cell dose level and a 38% CBR across all four dose levels evaluated (Figure 2).
Previous report
Figure 1: Best response of the target lesions for the 16 efficacy evaluable patients. The dark purple bars represent the target lesion tumor size reduction from baseline observed in patients treated at the 150 million cell dose level. Of the five patients with TNBC treated with LYL797 at this dose level, two patients had confirmed partial responses to Day 90, resulting in an ORR of 40%.
Previous report
Figure 2: A pattern of dose-dependent clinical activity emerged when the data were plotted by dose and clinical benefit rate, defined as stable disease, partial response or complete response. In addition to having stable disease by imaging, several patients had additional observations of clinical benefit including weight gain, decreased pain and improved liver function tests.
Previous report
◦The most frequently reported related adverse events of any grade were cytokine release syndrome (CRS) (61%), pneumonitis (22%) and headache (17%), as well as the expected cytopenia from lymphodepletion in all patients. The CRS was generally mild (Grade 1 or 2 only), characterized by fever and treated with tocilizumab and steroids. There were no reports of immune effector cell-associated neurotoxicity syndrome (ICANS) attributed to LYL797. The most frequently reported Grade> 3 related adverse events were pneumonitis (17%) and hypoxia (11%), as well as the expected cytopenia from lymphodepletion in 78% of patients. The index patient with pneumonitis had Grade 5 respiratory failure on Day 41. Subsequently, patients were treated aggressively at the first sign or symptom of pneumonitis with high‑dose steroids with good result. Each case of pneumonitis has occurred between days 4 and 10. The adverse event of Grade> 3 pneumonitis occurred only in patients with TNBC and lung metastases, resulting in the separation of dose escalation into two cohorts based upon lung involvement (lung primary, lung metastatic disease or pleural effusion). No dose-limiting toxicities occurred in patients without lung involvement. All patients are now receiving prophylactic therapy with dexamethasone to mitigate pneumonitis.
Previous report
◦Translational data were reported on a subset of patients and include CAR T-cell expansion in peripheral blood, phenotypic analysis of T-cell exhaustion and stem-like markers, and on-study tumor biopsies to assess for CAR T-cell tumor infiltration. LYL797 CAR T-cell expansion was observed in peripheral blood samples at Day 60 in all patients assessed when the data were reported (n = 11), with peak expansion occurring between Days 8 and 11. Peak expansion was on average three-fold higher in patients receiving 150 x 106 cells compared to those receiving 50 x 106 cells. The exhaustion marker, TIGIT, was found only in a low proportion of LYL797 CAR T cells at Day 11 (n = 4) providing support for the role of c-Jun overexpression as an anti-exhaustion technology. A significant proportion of cells with stem-like and effector memory phenotypes were demonstrated at Days 11 and 22 following RNAseq transcriptomic analysis, supporting the role of Epi-R to preserve a stem-like phenotype. Nine evaluable on-treatment tumor biopsies collected between Days 21 and 30 after LYL797 infusion were assessed. LYL797 CAR T cells were present in all solid-tumor biopsies, indicating that LYL797 CAR T cells enhanced with our anti-exhaustion technology were able to infiltrate and persist in the solid tumor microenvironment. In addition, the tumor biopsies have features consistent with T cell-mediated tumor lysis, including T cell-rich inflammation with scattered tumor cells.
Previous report
•Updated data from the ongoing Phase 1 trial in solid tumor indications, including the initiation of dose expansion, are expected in late 2024 to early 2025.
Previous report
•An IND is expected to be filed in the second half of 2024 to initiate a Phase 1 trial of LYL797 in patients with relapsed/refractory multiple myeloma or CLL.
Previous report
LYL845 - A TIL product candidate epigenetically reprogrammed using Lyell’s proprietary Epi-R manufacturing protocol, designed for differentiated potency and durability
Previous report
We are applying our epigenetic reprogramming technology, Epi‑R, to develop LYL845, which is expected to be an intravenously‑administered autologous TIL therapy for multiple solid tumors. Our Epi‑R manufacturing protocol comprises proprietary media, optimized cytokine compositions and well-defined cell activation and expansion protocols used during our manufacturing process.
Previous report
TIL have previously shown clinical benefit in patients with advanced melanoma and other solid tumors with high mutational burden. Published data from third-party TIL trials show that treating metastatic melanoma patients with TIL can result in complete and durable responses. Response rates to TIL therapy in patients with other advanced solid tumors such as lung, colorectal and breast have been much lower than those observed in advanced melanoma. Broad TIL efficacy has been limited by poor enrichment of tumor-reactive T cells and the poor quality and limited growth potential of expanded T cells. Failure to maintain polyclonality of TIL during production may also limit their ability to eradicate cancer cells given the inherent heterogeneous nature of solid tumors. LYL845 incorporates our Epi‑R technology that has shown promising improvements in enhancing T-cell phenotypes reported in the literature to be associated with improved clinical outcomes (Krishna et al., Science, Dec. 2020), antitumor activity and increased polyclonality of TIL with stem-like qualities in nonclinical experiments. We received Orphan Drug Designation for LYL845 as a potential novel treatment for patients with advanced melanoma.
Previous report
We are initially developing LYL845 for advanced melanoma, NSCLC and colorectal cancer (CRC). Based on our success with those indications, we may include patients with other solid tumors, potentially including head and neck, cervical, breast and pancreatic cancer.
Previous report
•Enrollment in the Phase 1 clinical trial for LYL845 is ongoing. The study is designed to include patients with relapsed or refractory metastatic or locally advanced melanoma, NSCLC and CRC.
Previous report
•The Phase 1 clinical trial is an open-label, dose-escalation and -expansion trial in patients with relapsed or refractory metastatic or locally advanced melanoma, NSCLC and CRC. The study will enroll at least 15 patients each with advanced melanoma, and relapsed or refractory NSCLC or CRC in the expansion phase of the study.
Previous report
•Initial clinical and translational data from the Phase 1 trial of LYL845 in patients with advanced melanoma are expected in the second half of 2024.
Previous report
A key pillar of our strategy is to continually innovate to develop and advance novel, breakthrough technologies that address key barriers to effective cell therapy for solid tumors. We have advanced a new genetic reprogramming technology, NR4A3 knockout, and a new epigenetic reprogramming technology, Stim‑R, that are being applied in our new CAR T-cell product candidate, LYL119. These technologies are stackable and complementary to c-Jun and Epi‑R and are designed to enable T cells to further resist exhaustion and to improve antitumor potency and durability.
Previous report
LYL119 is being advanced with the goal of potentially creating even greater benefit for patients with ROR1‑positive solid tumors.
Previous report
•An IND application for LYL119 was cleared by the FDA.
Previous report
Three and Six Months Ended June 30, 2024 and 2023
Previous report
Other operating income, net was $1.0 million and $0.6 million for the three months ended June 30, 2024 and 2023, respectively, and $2.1 million and $1.9 million for the six months ended June 30, 2024 and 2023, respectively.
Reworded paragraphs (26)
Previous wording
We are a clinical-stage cell therapy company advancing a pipeline of product candidates enhanced with our proprietary anti-exhaustion technologies for patients with solid tumors or hematologic malignancies. 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 resist exhaustion and kill cancer cells. Our innovative genetic and epigenetic 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. We apply our technologies with the aim of developing T‑cell therapies with improved and durable antitumor responses for patients. 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.
Current wording
We are a clinical-stage cell therapy company advancing a pipeline of proprietary next-generation chimeric antigen receptor (CAR) T-cell product candidates for patients with solid tumors or hematologic malignancies. We have developed novel technologies and manufacturing protocols designed to generate T cells that resist exhaustion and have qualities of durable stemness to drive durable tumor cytotoxicity and achieve consistent and long-lasting clinical responses. Our investigational therapies use the patient’s own living cells as the starting point. We incorporate our innovative technology and manufacturing protocols to expand and activate the patient’s T cells. Our technologies are designed to generate highly tumor‑reactive, longer-lasting functional T cells with enhanced ability to persist, self‑renew and kill cancer cells over time. Our technology can be applied in a target agnostic manner to multiple T‑cell modalities, including CAR, tumor-infiltrating lymphocytes (TIL) and T‑cell receptor (TCR) therapies.
Previous wording
Our growing pipeline of promising cell product candidates target indications with large unmet needs that are collectively responsible for approximately 224,000 deaths in the United States annually. Our programs provide opportunities to expand into additional indications beyond the patient populations we are targeting. Our lead product candidates are summarized in Table 1 below:
Current wording
Our pipeline of next-generation CAR T-cell product candidates target indications with large unmet need and provide opportunities to expand into additional indications beyond the patient populations we are initially evaluating. Our lead product candidates are summarized in Table 1 below:
Previous wording
We were incorporated in June 2018. Our primary activities to date have included clinical development of T‑cell therapies, conducting research and development, acquiring technology, entering into strategic collaboration and license agreements, enabling and executing manufacturing activities in support of our product candidate development efforts, organizing and staffing our company, business planning, establishing our intellectual property portfolio, making regulatory submissions, executing clinical trials, raising capital and providing general and administrative support for these activities. We are early in our research and development efforts. LYL797, our ROR1‑targeted CAR T‑cell product candidate, is in Phase 1 clinical development for multiple solid tumor indications, and we expect to initiate a second Phase 1 clinical trial of LYL797 for hematologic indications in the second half of 2024. LYL119, our next generation ROR1‑targeted CAR T‑cell product candidate, is entering Phase 1 clinical trial in patients with solid tumors in the second half of 2024; and LYL845, our TIL product candidate, is in Phase 1 clinical development. A second generation TIL product candidate enhanced with novel genetic and epigenetic reprogramming technologies is in preclinical development. We do not have any products approved for sale.
Current wording
We were incorporated in June 2018. Our primary activities to date have included clinical development of T‑cell therapies, conducting research and development, acquiring technology and product candidates, entering into strategic collaboration and license agreements, enabling and executing manufacturing activities in support of our product candidate development efforts, organizing and staffing our company, business planning, establishing our intellectual property portfolio, making regulatory submissions, executing clinical trials, raising capital and providing general and administrative support for these activities. We are early in our research and development efforts.
Previous wording
LYL119 - A next-generation ROR1-targeted CAR T-cell product candidate incorporating Lyell’s four stackable and complementary anti-exhaustion technologies designed for enhanced potency
Current wording
LYL119 - A next-generation ROR1-targeted CAR T-cell product candidate enhanced with Lyell’s four stackable and complementary anti-exhaustion technologies
Previous wording
We are applying our c-Jun and Epi‑R technologies to our lead CAR T‑cell product candidate, LYL797, which is an intravenously‑administered autologous CAR T‑cell investigational product targeting the receptor tyrosine kinase-like orphan receptor 1 (ROR1) protein. ROR1 is a fetal protein expressed during embryogenesis and is believed to be important in cell migration, polarity and survival. It is expressed in several cancer types, including triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), ovarian cancer, endometrial cancer, multiple myeloma and chronic lymphocytic leukemia (CLL), and is generally associated with a poor prognosis. LYL797 contains a CAR with a 4‑1BB/CD3ζ intracellular domain, a transmembrane domain, an optimized spacer domain and a single-chain variable fragment (scFv) derived from an R12 rabbit monoclonal antibody that recognizes and binds with high specificity to human ROR1. LYL797 also incorporates c-Jun and a proprietary optimized truncated version of human EGFR (EGFRopt) used for tracking the CAR T cells in the peripheral blood post treatment and can also be used as a safety measure with the administration of cetuximab, if needed. LYL797 is manufactured utilizing Epi‑R, our proprietary ex vivo manufacturing protocol that is designed to generate populations of T cells with stem-like qualities, reduced exhaustion and improved proliferation and antitumor activity.
Current wording
LYL119 is an autologous CAR T‑cell investigational product targeting the receptor tyrosine kinase-like orphan receptor 1 (ROR1) protein and enhanced with four of Lyell’s novel reprogramming technologies: c-Jun overexpression, NR4A3 knockout, Epi-R manufacturing protocol and Stim‑RTM T-cell activation technology. These technologies are stackable and complementary and are designed to enable T cells to resist exhaustion and to improve antitumor potency and durability. LYL119 targets ROR1, a fetal protein expressed during embryogenesis and is believed to be important in cell migration, polarity and survival. Significant subsets of patients with common cancers express ROR1, including ovarian cancer, endometrial cancer, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC) and chronic lymphocytic leukemia (CLL), and is generally associated with a poor prognosis.
Previous wording
Based on initial clinical data that demonstrated dose-dependent anti-tumor activity, we expanded the Phase 1 trial to include patients with platinum-resistant ovarian and endometrial cancers, where it is estimated in the literature that approximately 50% of patients have tumors in both indications that express ROR1. Ovarian cancer is one of the leading causes of cancer deaths among women. In the United States, approximately 20,000 women will be newly diagnosed with ovarian cancer in 2024. Only about 20% of ovarian cancers are diagnosed at an early stage. Late‑stage diagnosis is due in part to the largely asymptomatic nature of early‑stage disease and a lack of effective screening methods, coupled with the tumor’s inherent aggressive biology. Only 30% of advanced stage ovarian cancer patients survive for five years after initial diagnosis. Endometrial cancer (cancer of the lining of the uterus) is the most prevalent gynecological cancer and the sixth most common malignancy worldwide. Its incidence has been increasing over the last decade and it is one of the few cancers with increasing mortality. In 2024 in the United States, approximately 68,000 women will be newly diagnosed with uterine cancer, which includes patients with endometrial cancers and uterine sarcomas that together account for approximately 10% of uterine cancers. Only 19% of advanced stage endometrial cancer patients survive for five years after initial diagnosis.
Current wording
The Phase 1 trial of LYL119 will initially include patients with platinum-resistant ovarian and endometrial cancers, where it is estimated in the literature that approximately 50% of patients have tumors in both indications that express ROR1.
Previous wording
•The Phase 1 trial is designed as an open label dose escalation and expansion trial in patients with ROR1 positive solid tumors and will initially enroll patients with ROR1 positive platinum-resistant ovarian cancer or endometrial cancer. Initial clinical data are expected in the second half of 2025.
Current wording
•The Phase 1 trial of LYL119 is designed as an open label dose escalation and expansion trial in patients with ROR1‑positive solid tumors and will initially enroll patients with ROR1‑positive platinum-resistant ovarian cancer or relapsed/refractory endometrial cancer. LYL119 is expected to enroll its first patient later this year or early next year and initial clinical data are expected in the second half of 2025.
Previous wording
We recently reported initial clinical and translational data from our ongoing Phase 1 trial, detailed below. We believe these initial clinical and translational data (1) demonstrated that T-cell exhaustion is a key barrier to cell therapy in solid tumors as elucidated by the Fred Hutch Cancer Center study, and (2) provided early validation of our in vivo preclinical models demonstrating that LYL797 ROR-1 CAR T cells reprogrammed with our c-Jun overexpression and Epi‑R anti-exhaustion technology enhanced tumor control resulting in prolonged survival as compared to control ROR1 CAR T cells without our technologies.
Current wording
In June 2024, we reported initial clinical and translational data from our Phase 1 trial of LYL797, our first-generation ROR1‑targeting CAR T-cell product candidate enhanced with c-Jun overexpression and manufactured with Epi‑R protocol. These initial clinical data demonstrated dose-dependent clinical activity, including a 40% objective response rate at the 150 x 106 cell dose level, robust cell expansion and histologic evidence of CAR T-cell infiltration into on study tumor biopsies. In this study, CRS was generally mild (Grade 1 or 2 only), and there were no reports of ICANS attributed to LYL797. Pneumonitis was the most frequently reported Grade >3 related adverse event (17%) as well as the expected cytopenia from lymphodepletion (78%). Our manufacturing success was 100%. We believe these initial clinical and translational data provide early validation of our in vivo preclinical models. In our in vivo studies LYL797 ROR1 CAR T cells reprogrammed with our c-Jun overexpression and Epi-R anti-exhaustion technology enhanced tumor control resulting in prolonged survival as compared to control ROR1 CAR T cells without our technologies. Translational data from the LYL797 Phase 1 clinical trial are being presented at the 39th Annual Meeting of SITC in November 2024.
Previous wording
Our LyFE Manufacturing Center™ located in Bothell, Washington is approximately 73,000 square feet and is comprised of manufacturing suites, laboratories and offices. Our LyFE Manufacturing Center was designed to be in compliance with U.S. and European Union current Good Manufacturing Practices (cGMP) standards and has a flexible and modular design enabling CAR T-cell, TIL, TCR T-cell and cGMP viral vector production to control and de-risk the manufacturing sequence and timing of the major components of our supply chain. Owning our own facility has enabled seamless collaboration across research, process development and manufacturing for high-quality reproducibility at manufacturing scale.
Current wording
Our LyFE Manufacturing Center™ (LyFE) located in Bothell, Washington is approximately 73,000 square feet and is comprised of manufacturing suites, laboratories and offices. Our LyFE Manufacturing Center was designed to be in compliance with U.S. and European Union current Good Manufacturing Practices (cGMP) standards and has a flexible and modular design enabling CAR T-cell, TIL, TCR T-cell and cGMP viral vector production to control and de-risk the manufacturing sequence and timing of the major components of our supply chain. Owning our own facility has enabled seamless collaboration across research, process development and manufacturing for high-quality reproducibility at manufacturing scale. Clinical supply for our Phase 1 trial of LYL119 will be produced at LyFE and clinical supply for our Phase 1-2 trial of IMPT-314 is currently manufactured in our wholly-owned manufacturing facility in Los Angeles, California, that we acquired in connection with the acquisition of ImmPACT. As we accelerate development of IMPT-314, we expect to supplement our Los Angeles manufacturing capacity and will evaluate options either at LyFE or through a contract development manufacturing organization. We are focused on maintaining a manufacturing strategy that is operationally efficient to maximize our capacity and avoid any disruption to clinical trial supply.
Previous wording
We are currently producing clinical supply for our Phase 1 trials at our LyFE Manufacturing Center. At full staffing and capacity, we expect to be able to manufacture approximately 500 infusions per year depending on product candidate mix. While we believe this capacity is sufficient to support our pipeline programs into pivotal trials and, if approved, early commercialization, we are also advancing multiple strategic alternatives to innovate and scale manufacturing in the future. We are evaluating third-party manufacturing options as part of an overall CAR T‑cell manufacturing strategy to build scale and reduce cost. For TIL, we are advancing our Epi-R P2 manufacturing protocol to shorten delivery time of TIL product to patients.
Current wording
At full staffing and capacity, we expect to be able to manufacture approximately 1,000 CAR T-cell products per year at LyFE depending on product candidate mix. While we believe this capacity is sufficient to support our pipeline programs into pivotal trials and, if approved, early commercialization, we are also advancing multiple strategic alternatives to innovate and scale manufacturing in the future. We are evaluating third-party manufacturing options as part of an overall CAR T‑cell manufacturing strategy to build scale and reduce cost.
Previous wording
Research and development expenses also include non-cash expenses related to the change in the estimated fair value of the success payment obligations over their respective requisite service terms granted to Fred Hutchinson Cancer Center (Fred Hutch) and The Board of Trustees of the Leland Stanford Junior University (Stanford). As of December 31, 2022, Fred Hutch had provided the requisite service obligation to earn the potential success payment consideration under the continued collaboration. For the three and six months ended June 30, 2023 and future periods, the change in the Fred Hutch success payment liability fair value is recognized in other (expense) income, net, as the requisite service obligation had been met. See Note 3, License, Collaboration and Success Payment Agreements, in the accompanying notes to the unaudited Condensed Consolidated Financial Statements included in Part I, Item 1 of this Quarterly Report on Form 10‑Q. Research and development expenses related to our success payment liabilities are unpredictable and may vary significantly from quarter‑to‑quarter and year‑to‑year due to changes in our assumptions used in the calculation.
Current wording
Research and development expenses also include non-cash expenses related to the change in the estimated fair value of the success payment obligations over their respective requisite service terms granted to Fred Hutchinson Cancer Center (Fred Hutch) and The Board of Trustees of the Leland Stanford Junior University (Stanford). As of December 31, 2022, Fred Hutch had provided the requisite service obligation to earn the potential success payment consideration under the continued collaboration. For the three and nine months ended September 30, 2023 and future periods, the change in the Fred Hutch success payment liability fair value is recognized in other (expense) income, net, as the requisite service obligation had been met. See Note 3, License, Collaboration and Success Payment Agreements, in the accompanying notes to the unaudited Condensed Consolidated Financial Statements included in Part I, Item 1 of this Quarterly Report on Form 10‑Q. Research and development expenses related to our success payment liabilities are unpredictable and may vary significantly from quarter‑to‑quarter and year‑to‑year due to changes in our assumptions used in the calculation.
Previous wording
Research and development expenses were $83.4 million and $92.1 million for the six months ended June 30, 2024 and 2023, respectively. The $8.7 million decrease was primarily due to a $9.4 million reduction in personnel-related expenses mainly due to a decrease in headcount associated with the Company’s November 2023 reduction in workforce; a decrease of $1.9 million in facilities and technology costs primarily driven by the reduction in workforce and lower software implementation costs; and a decrease of $0.3 million associated with our success payment liabilities primarily driven by the change in our stock price. These decreases were partially offset by an increase of $2.9 million in research activities, collaborations and outside services primarily driven by clinical trials activity.
Current wording
Research and development expenses were $39.5 million and $43.8 million for the three months ended September 30, 2024 and 2023, respectively. The $4.3 million decrease was primarily due to a $4.9 million reduction in personnel‑related expenses, mainly due to a decrease in headcount associated with the Company’s November 2023 reduction in workforce. These decreases were partially offset by a change of $1.2 million in success payment expense primarily driven by the change in our stock price.
Previous wording
Research and development expenses were $40.3 million and $47.5 million for the three months ended June 30, 2024 and 2023, respectively. The $7.2 million decrease was primarily due to a $6.2 million reduction in personnel‑related expenses, mainly due to a decrease in headcount associated with the Company’s November 2023 reduction in workforce; a decrease of $1.7 million in facilities and technology costs primarily driven by the reduction in workforce and lower software implementation costs; and a decrease of $1.4 million associated with our success payment liabilities primarily driven by the change in our stock price. These decreases were partially offset by an increase of $2.0 million in research activities, collaborations and outside services primarily driven by clinical trials activity.
Current wording
Research and development expenses were $122.9 million and $136.0 million for the nine months ended September 30, 2024 and 2023, respectively. The $13.0 million decrease was primarily due to a $14.2 million reduction in personnel-related expenses mainly due to a decrease in headcount associated with the Company’s November 2023 reduction in workforce and a decrease of $2.6 million in facilities and technology costs primarily driven by the reduction in workforce and lower software implementation costs. These decreases were partially offset by an increase of $2.8 million in research activities, collaborations and outside services primarily driven by clinical trials activity and a change of $0.9 million in success payment expense primarily driven by the change in our stock price.
Previous wording
General and administrative expenses were $12.3 million and $19.0 million for the three months ended June 30, 2024 and 2023, respectively. The $6.8 million decrease was primarily due to a $6.5 million reduction in personnel costs, including a $4.5 million decrease in stock-based compensation expense, primarily related to significant awards being fully expensed in the previous periods and a decrease of $2.0 million in personnel‑related expenses mainly due to a decrease in headcount associated with the Company’s November 2023 reduction in workforce.
Current wording
General and administrative expenses were $11.8 million and $15.5 million for the three months ended September 30, 2024 and 2023, respectively. The $3.7 million decrease was primarily due to a $3.3 million reduction in personnel costs, including a $2.0 million decrease in stock-based compensation expense, primarily related to significant awards being fully expensed in the previous periods and a decrease of $1.4 million in personnel‑related expenses mainly due to a decrease in headcount associated with the Company’s November 2023 reduction in workforce.
Previous wording
General and administrative expenses were $25.8 million and $38.3 million for the six months ended June 30, 2024 and 2023, respectively. The $12.6 million decrease was primarily due to a $11.2 million reduction in personnel costs, including a $8.4 million decrease in stock-based compensation expense, primarily related to significant awards being fully expensed in the previous periods and a decrease of $2.8 million in personnel-related expenses mainly due to a decrease in headcount associated with the Company’s November 2023 reduction in workforce. General and administrative expenses also decreased due to a reduction of $1.2 million in other administrative expenses.
Current wording
General and administrative expenses were $37.5 million and $53.8 million for the nine months ended September 30, 2024 and 2023, respectively. The $16.3 million decrease was primarily due to a $14.6 million reduction in personnel costs, including a $10.4 million decrease in stock-based compensation expense, primarily related to significant awards being fully expensed in the previous periods and a decrease of $4.1 million in personnel-related expenses mainly due to a decrease in headcount associated with the Company’s November 2023 reduction in workforce. General and administrative expenses also decreased due to a reduction of $1.6 million in other administrative expenses.
Previous wording
Interest income, net was $6.4 million and $5.3 million for the three months ended June 30, 2024 and 2023, respectively, and $13.2 million and $9.8 million for the six months ended June 30, 2024 and 2023, respectively. The increase in interest income, net was primarily driven by higher interest rates in 2024.
Current wording
Interest income, net was $6.0 million and $6.6 million for the three months ended September 30, 2024 and 2023, respectively, and $19.1 million and $16.4 million for the nine months ended September 30, 2024 and 2023, respectively. The increase in interest income, net for the nine months ended September 30, 2024 was primarily driven by higher interest rates in 2024.
Previous wording
Other (expense) income, net was $(0.6) million and $(0.3) million for the three months ended June 30, 2024 and 2023, respectively, and $0.4 million and $0.8 million for the six months ended June 30, 2024 and 2023, respectively. Other (expense) income, net consists primarily of the change in fair value associated with our success payment liabilities to Fred Hutch and for the three and six months ended June 30, 2024, adjustments to the fair value of our marketable equity security investment that is publicly traded.
Current wording
Other (expense) income, net was approximately zero and $1.6 million for the three months ended September 30, 2024 and 2023, respectively, and $0.4 million and $2.4 million for the nine months ended September 30, 2024 and 2023, respectively. Other (expense) income, net consists primarily of the change in fair value associated with our success payment liabilities to Fred Hutch and for the three and nine months ended September 30, 2024, also includes adjustments to the fair value of our marketable equity security investment that is publicly traded.
Previous wording
Impairment of other investments waszero for the three months ended June 30, 2024 and $2.9 million for the three months ended June 30, 2023, which consisted of the full impairment of one of our other investments. Impairment of other investments was $13.0 million and $12.9 million for the six months ended June 30, 2024 and 2023, respectively, which consisted of the full impairment of one of our other investments for the six months ended June 30, 2024 and the full impairment of two of our other investments for the six months ended June 30, 2023. See Note 5, Other Investments, in the accompanying notes to the unaudited Condensed Consolidated Financial Statements included in Part I, Item 1 of this Quarterly Report on Form 10‑Q, for additional details regarding the impairments of other investments.
Current wording
Impairment of other investments was zero for both the three months ended September 30, 2024 and 2023, and $13.0 million and $12.9 million for the nine months ended September 30, 2024 and 2023, respectively, which consisted of the full impairment of one of our other investments for the nine months ended September 30, 2024 and the full impairment of two of our other investments for the nine months ended September 30, 2023. See Note 5, Other Investments, in the accompanying notes to the unaudited Condensed Consolidated Financial Statements included in Part I, Item 1 of this Quarterly Report on Form 10‑Q, for additional details regarding the impairments of other investments.
Previous wording
As of June 30, 2024, we had $491.1 million in cash, cash equivalents and marketable securities. To date we have raised an aggregate of $1.4 billion in gross proceeds from sales of common stock and convertible preferred stock.
Current wording
As of September 30, 2024, we had $460.7 million in cash, cash equivalents and marketable securities. To date we have raised an aggregate of $1.4 billion in gross proceeds from sales of common stock and convertible preferred stock.
Previous wording
We continually evaluate our liquidity and capital resources to ensure that we can adequately and efficiently finance our operations. As of June 30, 2024, 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 7, Leases, in the accompanying notes to the unaudited Condensed Consolidated Financial Statements included in Part I, Item 1 of this Quarterly Report on Form 10-Q, for additional information.
Current wording
We continually evaluate our liquidity and capital resources to ensure that we can adequately and efficiently finance our operations. As of September 30, 2024, our material cash requirements consisted primarily of paying salaries and benefits, administering clinical trials, conducting research, manufacturing products for our clinical trials, 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 7, Leases, in the accompanying notes to the unaudited Condensed Consolidated Financial Statements included in Part I, Item 1 of this Quarterly Report on Form 10-Q, for additional information.
Previous wording
During the six months ended June 30, 2024, net cash used in operating activities was $80.1 million, reflecting our net loss of $106.5 million, partially offset by $30.6 million of non-cash items primarily related to stock-based compensation expense of $17.4 million, the impairment of other investments of $13.0 million and depreciation and amortization expense of $9.9 million, partially offset by net amortization and accretion on marketable securities of $8.1 million and non-cash lease income of $1.0 million. Additionally, net operating assets and liabilities decreased $4.2 million primarily driven by a $3.1 million decrease in accrued liabilities and other current liabilities and a $0.6 million decrease in accounts payable.
Current wording
During the nine months ended September 30, 2024, net cash used in operating activities was $115.2 million, reflecting our net loss of $151.1 million, partially offset by $39.1 million of non-cash items primarily related to stock-based compensation expense of $25.1 million, depreciation and amortization expense of $14.6 million and the impairment of other investments of $13.0 million, partially offset by net amortization and accretion on marketable securities of $11.7 million and non-cash lease income of $1.6 million. Net operating assets and liabilities decreased by $3.2 million, which also contributed to the net cash used in operating activities.
Previous wording
During the six months ended June 30, 2023, net cash used in operating activities was $85.4 million, primarily reflecting our net loss of $130.8 million, partially offset by $46.2 million of non-cash items primarily related to stock-based compensation expense of $28.1 million, impairment of other investments of $12.9 million and depreciation and amortization of $10.1 million, partially offset by net amortization and accretion on marketable securities of $3.9 million and non-cash lease income of $0.8 million. Additionally, net operating assets and liabilities decreased $0.7 million primarily driven by a $3.6 million decrease in accrued liabilities and other current liabilities partially offset by a $2.4 million increase in accounts payable.
Current wording
During the nine months ended September 30, 2023, net cash used in operating activities was $123.1 million, primarily reflecting our net loss of $181.7 million, partially offset by $56.9 million of non-cash items primarily related to stock-based compensation expense of $38.6 million, depreciation and amortization of $15.2 million and impairment of other investments of $12.9 million. Non-cash net amortization and accretion on marketable securities of $6.2 million also contributed to net cash used in operating activities.
Previous wording
During the six months ended June 30, 2024, cash provided by investing activities was $67.0 million, consisting primarily of net maturities and purchases of marketable securities.
Current wording
During the nine months ended September 30, 2024, cash provided by investing activities was $68.9 million, consisting primarily of net maturities and purchases of marketable securities.
Previous wording
During the six months ended June 30, 2023, cash provided by investing activities was $185.1 million, consisting of net maturities and purchases of marketable securities of $187.5 million offset by purchases of property and equipment of $2.5 million.
Current wording
During the nine months ended September 30, 2023, cash provided by investing activities was $284.7 million, consisting of net maturities and purchases of marketable securities of $287.4 million offset by purchases of property and equipment of $2.7 million.
Previous wording
During the six months ended June 30, 2024, cash provided by financing activities was $0.9 million, consisting of proceeds from the employee stock purchase plan of $0.8 million and proceeds from the exercise of stock options of $0.2 million, partially offset by taxes paid related to the net share settlement of equity awards of $0.1 million.
Current wording
During the nine months ended September 30, 2024, cash provided by financing activities was $0.9 million, consisting of proceeds from the employee stock purchase plan of $0.8 million and proceeds from the exercise of stock options of $0.2 million, partially offset by taxes paid related to the net share settlement of equity awards of $0.1 million.
Previous wording
During the six months ended June 30, 2023, cash provided by financing activities was $1.1 million, consisting of proceeds from the employee stock purchase plan of $1.2 million and proceeds from the exercise of stock options of $0.1 million, partially offset by taxes paid related to the net share settlement of equity awards of $0.1 million.
Current wording
During the nine months ended September 30, 2023, cash provided by financing activities was $1.0 million, consisting of proceeds from the employee stock purchase plan of $1.2 million and proceeds from the exercise of stock options of $0.2 million, partially offset by taxes paid related to the net share settlement of equity awards of $0.3 million.
Rearranged previous paragraphs (1)
Previous report — wording carried elsewhere
•LYL119 is a ROR1-targeted CAR T-cell product enhanced with Lyell’s four novel genetic and epigenetic reprogramming technologies: c-Jun overexpression, NR4A3 knockout, Epi-R manufacturing protocol and Stim‑RTM T-cell activation technology.