Business Overview Instil Bio's journey began in August 2018 when the company was incorporated in the state of Delaware. The founders set out with the ambitious goal of developing a pipeline of novel cancer therapies. Initially, the company's strategy was primarily focused on the development of its proprietary folate receptor alpha (FRα) co-stimulatory antigen receptor (CoStAR) tumor infiltrating lymphocyte (TIL) cell therapy technology for the treatment of cancer.
In February 2019, Instil Bio made a significant move by entering into a license agreement with Immetacyte Ltd., obtaining a worldwide license to Immetacyte's proprietary TIL therapy technology, know-how, and intellectual property. This was followed by a strategic acquisition in March 2020, when Instil Bio acquired 100% of the share capital of Immetacyte. This acquisition allowed Instil Bio to terminate the previous license agreement and consolidate the TIL therapy technology under its ownership, strengthening its position in the field.
The company's initial clinical development efforts centered around its ITIL-168 program, a TIL therapy for the treatment of PD-1 inhibitor-relapsed or refractory advanced cutaneous melanoma. However, in 2022, Instil Bio encountered manufacturing and other challenges that led to a voluntary pause in its ITIL-168 clinical trials. Subsequently, in January 2023, the company made the difficult decision to discontinue the ITIL-168 development program.
From late 2022 through 2024, Instil Bio implemented several strategic reprioritizations and restructurings of its preclinical and clinical development programs. These actions resulted in the discontinuation of the company's TIL development efforts, including the ITIL-306 clinical trial, and a significant reduction in its workforce, both in the United States and the United Kingdom. This strategic pivot led to the company's current focus on the development of SYN-2510, a bispecific antibody targeting PD-L1 and VEGF, which it in-licensed from ImmuneOnco Biopharmaceuticals in August 2024.
In March 2021, Instil Bio took a significant step forward by completing its initial public offering (IPO), raising $339 million in gross proceeds. This infusion of capital allowed the company to accelerate the clinical development of its pipeline and expand its research and development capabilities.
Financial Snapshot Instil Bio's financial performance has been marked by significant investments in research and development, as the company has prioritized the advancement of its pipeline. As of the latest reported quarter, the company's cash, cash equivalents, marketable securities, and long-term investments totaled $122.9 million, providing a solid foundation for its ongoing operations and future development efforts.
In the third quarter of 2024, Instil Bio reported a net loss of $23.0 million, compared to a net loss of $67.4 million in the same period of the previous year. The company's research and development expenses for the quarter were $0.6 million, down from $8.5 million in the third quarter of 2023, reflecting the company's strategic shift away from its TIL program.
General and administrative expenses for the third quarter of 2024 were $10.7 million, down from $11.9 million in the same period of the previous year, as the company continued to streamline its operations and focus on its bispecific antibody pipeline.
It's important to note that Instil Bio has not yet generated any revenue from product sales, as its lead candidate, SYN-2510, is still in the early stages of clinical development. The company's future financial performance will be largely dependent on the successful advancement and commercialization of its pipeline.
For the first nine months of 2024, Instil Bio reported a net loss of $62.2 million. Research and development expenses for this period were $33.8 million, while general and administrative expenses were also $33.8 million. The company also reported restructuring and impairment charges of $7.1 million for the first nine months of 2024, reflecting the ongoing strategic changes within the organization.
Liquidity As of September 30, 2024, Instil Bio's liquidity position remained solid, with $122.9 million in cash, cash equivalents, marketable securities, and long-term investments. This financial cushion provides the company with runway to advance its pipeline and support ongoing operations. However, given the capital-intensive nature of biopharmaceutical development, Instil Bio will need to carefully manage its resources and may require additional funding in the future to support its long-term growth objectives.
The company's cash and cash equivalents stood at $6.66 million, with an additional $113.69 million in marketable securities. Instil Bio's debt-to-equity ratio was 0.008001950865412971, indicating a relatively low level of debt compared to equity. The company's current ratio and quick ratio were both 12.896206225680935, suggesting a strong ability to meet short-term obligations.
Instil Bio has a construction loan and mezzanine construction loan, with an outstanding principal amount of $82.80 million as of September 30, 2024. The company has agreed to terminate any undrawn commitments under these loans, limiting its additional borrowing capacity.
Pipeline and Collaborations Instil Bio's pipeline is anchored by its lead candidate, SYN-2510, a novel and differentiated PD-L1xVEGF bispecific antibody. The company in-licensed the global rights to SYN-2510, excluding China, from ImmuneOnco in August 2024. ImmuneOnco is currently conducting a Phase I clinical trial of SYN-2510 in China, and Instil Bio is planning to initiate a U.S. clinical study of the candidate in non-small cell lung cancer (NSCLC) in the second half of 2025.
In addition to SYN-2510, Instil Bio's pipeline includes SYN-27M, an antibody-dependent cellular cytotoxicity-enhanced monoclonal antibody targeting CTLA-4. ImmuneOnco has completed a first-in-human dose escalation study of SYN-27M in China and is currently pursuing cohort expansions of the recommended Phase 2 dose in patients with hormone receptor-positive breast cancer and hepatocellular carcinoma.
Instil Bio's collaboration with ImmuneOnco has been a critical component of its strategy. The companies are working together to advance the clinical development of SYN-2510 and SYN-27M, leveraging ImmuneOnco's expertise and data from its ongoing trials in China. This collaboration allows Instil Bio to potentially accelerate the development and regulatory approval process for these product candidates.
Additionally, Instil Bio has a collaboration with a third-party partner in China to develop an autologous folate receptor alpha (FRα) CoStAR-TIL cell therapy for a potential investigator-initiated trial in non-small cell lung cancer. This collaboration represents the company's continued efforts to advance its CoStAR-TIL technology through strategic partnerships.
Risks and Challenges Like any biopharmaceutical company, Instil Bio faces a variety of risks and challenges that could impact its long-term success. One of the primary risks is the inherent uncertainty and complexity associated with the development of novel cancer therapies. The company's SYN-2510 and SYN-27M candidates are still in early-stage clinical trials, and there is no guarantee that they will successfully navigate the regulatory approval process or achieve commercial success.
Furthermore, Instil Bio's reliance on third-party manufacturers, including ImmuneOnco, for the production of its product candidates introduces additional risks related to supply chain disruptions, quality control, and regulatory compliance. Any issues with these third-party partners could significantly delay the company's development and commercialization efforts.
The highly competitive nature of the oncology market also poses a significant challenge for Instil Bio. The company must contend with well-established pharmaceutical and biotechnology companies, as well as emerging players, in the race to develop and commercialize innovative cancer therapies.
Additionally, the company's ongoing restructuring and prioritization of its bispecific antibody platform represent a significant shift in its strategy, which carries inherent risks and uncertainties. The success of this pivot will be crucial in determining Instil Bio's long-term trajectory.
Outlook and Conclusion Instil Bio's transition from its TIL program to a greater focus on bispecific antibodies, exemplified by the in-licensing of SYN-2510, represents a strategic pivot that could unlock significant value for the company and its shareholders. The collaboration with ImmuneOnco provides access to clinical data and expertise that could accelerate the development of Instil Bio's lead candidate.
However, the company's success will ultimately hinge on the ability of SYN-2510 and its broader pipeline to navigate the rigorous clinical trial and regulatory approval processes, as well as the company's capacity to effectively manage its operations and partnerships.
As Instil Bio continues to execute on its revised strategy, investors will closely monitor the company's progress in advancing its bispecific antibody platform and its ability to effectively allocate capital to drive long-term growth. The competitive landscape and regulatory environment will also be critical factors in determining the company's future trajectory.
In conclusion, Instil Bio's journey as a clinical-stage biopharmaceutical company has been marked by both challenges and promising opportunities. The company's pivot to a bispecific antibody-focused strategy, anchored by the in-licensing of SYN-2510, presents a compelling growth story for investors willing to navigate the inherent risks and uncertainties of the oncology drug development landscape. With a solid cash position, a focused pipeline, and strategic collaborations in place, Instil Bio is positioned to potentially make significant strides in the development of novel cancer therapies in the coming years.