Financial Performance - For the three months ended September 30, 2024, the net loss was $23.0 million, and for the nine months ended September 30, 2024, the net loss was $62.2 million, with an accumulated deficit of $643.2 million as of September 30, 2024[100]. - Net loss for the three months ended September 30, 2024, was $23.0 million, a decrease of $52.9 million compared to a net loss of $67.4 million in the same period of 2023[116]. - The net loss for the nine months ended September 30, 2024, was $62.2 million, a decrease from a net loss of $143.2 million for the same period in 2023[144][145]. - The company incurred cash used in operating activities of $45.1 million for the nine months ended September 30, 2024, compared to $68.6 million for the same period in 2023, indicating a reduction of approximately 34.3%[143][145]. - Cash provided by financing activities for the nine months ended September 30, 2024, was $0.2 million, a significant decrease from $8.1 million in the same period of 2023[149]. Cash and Investments - As of September 30, 2024, the company had cash, cash equivalents, marketable securities, and long-term investments totaling $122.9 million, which includes $6.7 million in cash and cash equivalents[100]. - Cash provided by investing activities for the nine months ended September 30, 2024, was $41.0 million, an increase from $27.2 million in the same period of 2023, representing a growth of approximately 50.0%[146][147]. - The outstanding principal amount under the Loan as of September 30, 2024, was $82.8 million, with unamortized debt issuance costs of $0.7 million[133]. - Future funding requirements are anticipated to be met with existing cash and marketable securities, with potential opportunities for the sale of the Tarzana manufacturing site to extend cash runway[134]. Research and Development - The lead product candidate, SYN-2510, is a bispecific antibody targeting PD-L1 and VEGF, currently in a Phase I trial in China, with 65 patients dosed, showing a median age of 57 years and a median of 3 prior lines of therapy[91][93]. - Among 25 response evaluable patients treated with SYN-2510, 3 patients achieved confirmed partial responses, with tumor shrinkage of 46%, 32%, and over 53% respectively[95]. - Treatment-related adverse events occurred in 97% of patients, with the most common being infusion-related reactions (72.7%) and decreased platelet count (39.4%)[94]. - The recommended phase 2 dose for SYN-2510 was determined to be 20.0 mg/kg, with a half-life of approximately 6.8 days[96]. - The company is pursuing additional novel therapeutic candidates to address significant unmet medical needs in its pipeline[89]. Operating Expenses and Restructuring - Operating expenses for the three months ended September 30, 2024, were $23.6 million, a decrease of $53.1 million compared to $66.7 million in the same period of 2023[116]. - In-process research and development expenses increased by $10.0 million to $10.0 million for the three months ended September 30, 2024, primarily due to payments made to ImmuneOnco[117]. - Research and development expenses decreased by $7.9 million to $0.6 million for the three months ended September 30, 2024, mainly due to the discontinuation of ITIL-168 clinical manufacturing activities[118]. - General and administrative expenses decreased by $1.2 million to $10.7 million for the three months ended September 30, 2024, primarily due to reduced headcount[119]. - Restructuring and impairment charges decreased by $43.9 million to $2.4 million for the three months ended September 30, 2024, mainly due to a reduction in costs related to the impairment of the Tarzana manufacturing facility[120]. - The restructuring plan adopted in January 2023 resulted in a 96% reduction of the U.S. workforce and a 42% reduction of the UK workforce, incurring charges of $7.1 million for the nine months ended September 30, 2024[109]. - The company expects to incur additional restructuring and impairment charges in 2024 due to workforce reductions and other actions related to its 2024 Plan[121]. - The company plans to incur additional charges of up to $0.5 million in 2024 related to the 2024 Plan, which includes employee termination costs and contract termination costs[140]. Collaborations and Agreements - The company has entered into a collaboration for the development of an autologous folate receptor alpha CoStAR-TIL for a potential trial in non-small cell lung cancer in China[99]. - The company entered into an IO Collaboration Agreement with ImmuneOnco, involving an upfront payment of $10.0 million and potential payments up to $2.1 billion in milestones[138]. - The maximum contingent consideration remaining unpaid from the acquisition of Immetacyte was $13.3 million as of September 30, 2024[137].

Financial Performance - Instil Bio reported cash, cash equivalents, marketable securities, and long-term investments of $122.9 million as of September 30, 2024, down from $175.0 million as of December 31, 2023[7]. - The net loss for September 2024 was $23,021 thousand, a decrease from $67,432 thousand in September 2023[17]. - Non-GAAP net loss for September 2024 was $16,591 thousand, compared to $16,479 thousand in September 2023[17]. - Net loss per share was $3.54 for the three months ended September 30, 2024, down from $10.37 for the same period in 2023[10]. - Net loss per share for September 2024 was $(3.54), down from $(10.37) in September 2023[17]. - Non-GAAP net loss per share for September 2024 was $(2.55), slightly worse than $(2.53) in September 2023[17]. - The company incurred non-cash stock-based compensation expense of $4,068 thousand in September 2024, compared to $4,670 thousand in September 2023[17]. - Restructuring and impairment charges were $2,362 thousand in September 2024, significantly lower than $46,283 thousand in September 2023[17]. - General and administrative expenses were $10.7 million for the three months ended September 30, 2024, compared to $11.9 million for the same period in 2023[9]. - Research and development expenses decreased to $0.6 million for the three months ended September 30, 2024, from $8.5 million in the same period in 2023[8]. Research and Development - In-process research and development expenses were $10.0 million for both the three and nine months ended September 30, 2024, compared to nil for the same periods in 2023[8]. - Instil Bio licensed SYN-2510 for global development and commercialization outside of Greater China, marking a significant milestone for the company[2]. - Approximately 65 additional patients have been dosed with SYN-2510/IMM2510 in China, bringing the total to 98 patients[3]. - The initiation of Phase 1b/2 studies for SYN-2510/IMM2510 in combination with chemotherapy is expected in late 2024 and 1H 2025 in China[4]. - A U.S. clinical study of SYN-2510 in non-small cell lung cancer (NSCLC) is targeted for initiation in 2H 2025[5]. Cash Flow and Future Outlook - Instil Bio expects its cash resources to fund its operating plan beyond 2026[7]. - The weighted-average shares outstanding for basic and diluted were 6,506,681 in September 2024, a slight increase from 6,503,913 in September 2023[17].

Core Insights - Turnstone Biologics is advancing its next-generation Selected Tumor-Infiltrating Lymphocyte (TIL) technology aimed at selectively expanding potent tumor-reactive T cells for solid tumor treatment [1][5] - The company is presenting preclinical data at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting, showcasing methods for TIL selection [1][2] Company Overview - Turnstone Biologics is a clinical-stage biotechnology company focused on developing Selected TIL therapy to treat solid tumors, overcoming limitations of first-generation TIL therapies [5][6] - The clinical program TIDAL-01 is currently in multiple Phase 1 studies targeting colorectal cancer, head and neck cancer, and uveal melanoma [5][6] Research Findings - A study in collaboration with H. Lee Moffitt Cancer Center demonstrated successful TIL expansion from gastric tumors using tumor-specific neoantigens, enhancing adoptive cell therapy for solid tumors [3] - Another study in collaboration with the University of Montreal Hospital Research Centre indicated that the overlap between circulating and intratumoral T cell repertoires could predict the expansion of tumor-reactive TILs [4]

Core Insights - Instil Bio's shares have surged over six times in market value in the past week, driven by positive data from Summit Therapeutics' late-stage study on ivonescimab for non-small cell lung cancer (NSCLC) [1] - The phase III HARMONi-2 study demonstrated that ivonescimab significantly reduced the risk of disease progression or death by nearly half compared to Merck's Keytruda, with a median progression-free survival (PFS) of 11.14 months versus 5.82 months [2][3] - Instil Bio's stock performance has outpaced the industry, sector, and S&P 500, with a year-to-date increase of over 1,000% compared to the industry's 0.5% growth [8] Company Developments - Instil Bio entered a licensing and collaboration deal with ImmuneOnco, acquiring exclusive rights to develop and market two antibody treatments targeting cancer indications outside China [5] - One of the in-licensed candidates, SYN-2510, targets both PD-L1 and VEGF, potentially offering a competitive edge over ivonescimab, which only targets VEGF-A [6][7] - The company plans to prioritize the development of SYN-2510 in NSCLC and triple-negative breast cancer (TNBC), with plans to file an investigational new drug (IND) application with the FDA for a mid-stage study by the end of the year [10] Market Context - Analysts suggest that ivonescimab could replace Keytruda as the next standard of care in multiple NSCLC settings, highlighting the competitive landscape in the oncology market [6][4] - The dual mechanism of SYN-2510 may differentiate it from existing therapies, as it targets both PD-L1 and VEGF, which could lead to better outcomes in solid tumors [7]

Core Viewpoint - Instil Bio has experienced a significant stock price increase due to the in-licensing of IMM2510, a bispecific antibody, which is seen as a potential competitor to leading cancer therapies like Keytruda [2][3]. Company Developments - Instil Bio's shares surged approximately 235% from September 6 to September 12, raising its year-to-date gain to 510% [2]. - The company in-licensed IMM2510 in August, which targets PD-L1 and VEGF, shifting its focus from cell-based cancer therapies [3]. - Instil Bio's collaboration with ImmuneOnco Biopharmaceuticals is noteworthy, as a similar bispecific antibody, ivonescimab, has shown promising results in China [3]. Market Potential - Instil Bio's market capitalization has increased significantly, with analysts suggesting it could be undervalued given the potential of IMM2510 [4]. - Baird analyst Jack Allen raised the price target for Instil Bio to $180 per share, indicating a potential gain of 235% from its recent price [4]. Clinical Trials and Data - IMM2510 has not yet completed clinical trials, and initial studies have shown limited efficacy, with only three out of 25 patients experiencing tumor shrinkage [5]. - The comparison between IMM2510 and ivonescimab highlights potential differences in efficacy, but data is still limited [5]. Financial Position - Instil Bio leased a cell therapy manufacturing site to AstraZeneca for over $7.5 million annually, which will help reduce cash burn but not eliminate losses [6]. - The company ended June with $152.6 million in cash after a cash burn of $39.2 million in the first half of 2024, indicating a need for future capital raises [6]. Investment Considerations - Instil Bio represents a high-risk, high-reward investment opportunity, with potential for significant gains if clinical data for IMM2510 is positive [7]. - The stock is deemed suitable only for investors with a high tolerance for risk due to the uncertainties surrounding its clinical trials and financial needs [7].

Core Viewpoint - Instil Bio, Inc. has seen an increase in stock price following the in-licensing of ImmuneOnco's PD-L1/VEGF bispecific antibody IMM2510, which is positioned in a competitive and promising oncology market [1][2][7] Company Developments - Instil Bio in-licensed ex-China development and commercial rights to IMM2510, which allows commercialization outside Greater China, but incurs an upfront payment of $50 million and potential future costs exceeding $2 billion [2][5] - The company also acquired another candidate, IMM27M, an ADCC-enhanced anti-CTLA-4 antibody, which may enhance treatment efficacy when combined with IMM2510 [1][4] Competitive Landscape - The PD-1/VEGF bispecific antibody space is gaining traction, with competitors like Summit Therapeutics demonstrating clinically meaningful benefits in non-small cell lung cancer (NSCLC) [1][3] - IMM2510's unique ability to bind to all VEGF ligands and its superior ADCC killing capability may provide a competitive edge over existing therapies [1][3][4] Clinical Data - Clinical trials have shown that ivonescimab achieved a progression-free survival (PFS) of 11.4 months compared to Keytruda's 5.82 months, indicating the potential effectiveness of PD-L1/VEGF bispecific antibodies [3] - A phase 1 study of IMM2510 demonstrated safety with no dose-limiting toxicities observed across a range of doses [3][4] Financial Position - As of June 30, 2024, Instil Bio reported cash and equivalents of $152.6 million, supported by a successful IPO that raised $339 million [5] - The company has a cash burn rate of approximately $13.6 million per quarter, indicating a sufficient cash runway to fund operations beyond 2026 [5] Future Prospects - Instil Bio's strategy includes exploring combination therapies with IMM2510 and IMM27M, which may enhance treatment efficacy for solid tumors [4][7] - Analysts have raised price targets significantly, reflecting optimism about the company's potential in the oncology market [2][7]

In-licensed SYN-2510/IMM2510, a potentially best-in-class PD-L1xVEGF bispecific antibody, and SYN-27M/IMM27M, a next-generation ADCC-enhanced anti-CTLA-4 antibody Entered into a 15-year lease for our cell therapy manufacturing facility to AstraZeneca Pharmaceuticals LP DALLAS, Aug. 13, 2024 (GLOBE NEWSWIRE) -- Instil Bio, Inc. ("Instil") (Nasdaq: TIL), a clinical-stage biopharmaceutical company focused on developing a pipeline of novel therapies, today reported its second quarter 2024 financial results and ...

Core Viewpoint - Instil Bio has entered into a definitive agreement to in-license ex-China development and commercialization rights for ImmuneOnco's bispecific antibody IMM2510 and next-generation anti-CTLA-4 antibody IMM27M, indicating a strategic expansion in their oncology pipeline [1][4]. Group 1: Product Details - IMM2510 is a bispecific antibody that combines an anti-PD-L1 antibody with a VEGF receptor "trap," designed to enhance tumor penetration and improve tumor killing through enhanced antibody-dependent cellular cytotoxicity (ADCC) [2]. - IMM2510 has shown promising results in a dose-escalation clinical trial for advanced solid tumors, including responses in patients with squamous non-small cell lung cancer who had previously failed PD-1 inhibitors [2]. - IMM27M is a next-generation anti-CTLA-4 antibody with enhanced ADCC activity, aimed at improving efficacy and reducing toxicity compared to first-generation anti-CTLA-4 antibodies, and has also demonstrated anti-tumor activity in advanced solid tumors [3]. Group 2: Agreement Terms - Under the agreement, Instil's subsidiary will gain global rights for the development and commercialization of IMM2510 and IMM27M outside Greater China, while ImmuneOnco retains rights in Greater China, including Taiwan, Macau, and Hong Kong [4]. - ImmuneOnco will receive an upfront payment and potential near-term payments of up to $50 million, along with additional development, regulatory, and commercial milestones exceeding $2 billion, plus royalties on global ex-China sales [4]. Group 3: Company Background - Instil Bio is a clinical-stage biopharmaceutical company focused on developing novel therapies, with IMM2510 as its lead asset targeting multiple solid tumor cancers [5]. - ImmuneOnco is a clinical-stage biotech company dedicated to discovering and developing biologics for cancer treatment, currently advancing multiple assets, including one in phase III [6].

Core Insights - Instil Bio has entered into a definitive agreement to in-license ex-China development and commercialization rights for ImmuneOnco's bispecific antibody IMM2510 and next-generation anti-CTLA-4 antibody IMM27M [1][4] Group 1: Product Details - IMM2510 is a bispecific antibody that combines an anti-PD-L1 antibody with a VEGF receptor "trap," allowing it to bind multiple VEGF receptor ligands and potentially improve tumor penetration and efficacy [2] - IMM27M is designed to enhance ADCC activity and promote regulatory T cell depletion, aiming to improve efficacy and reduce toxicity compared to first-generation anti-CTLA-4 antibodies [3] Group 2: Clinical Development - IMM2510 has completed a dose-escalation clinical trial for advanced solid tumors, showing responses in patients with squamous non-small cell lung cancer who previously failed PD-1 inhibitors [2] - IMM27M has also completed a dose-escalation clinical trial and has entered combination studies with IMM2510 in China as of July 2024 [3] Group 3: Financial Terms - Under the agreement, Instil will pay an upfront fee and potential near-term payments totaling up to $50 million, along with additional milestone payments exceeding $2 billion and royalties on global ex-China sales [4]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 For the transition period from ________ to ________ 3963 Maple Avenue, Suite 350 Dallas, Texas Commission file number 001-40215 Instil Bio, Inc. FORM 10-Q (Exact name of registrant as specified in its charter) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 ...