Turnstone Biologics (TSBX) - 2023 Q4 - Annual Report

TIL Therapy Development - The company is developing next-generation tumor-infiltrating lymphocyte (TIL) therapies, focusing on Selected TILs for treating a wide range of solid tumors[18]. - The Selected TIL approach aims to achieve tumor-reactive T cell frequencies of up to 62%, with a median frequency of 23%, targeting over 70% in future products[24]. - The company’s proprietary approach to identifying tumor antigens aims to capture a comprehensive set of patient-specific antigens to drive robust T cell responses[24]. - The company aims to commercialize Selected TIL therapy by expanding in-house cell therapy processes and establishing a network of external manufacturing partners[49]. - The Selected TIL approach focuses on selecting and expanding potent tumor-reactive T cells to improve clinical responses in solid tumors where bulk TILs have been ineffective[59]. - TIDAL-01 aims to select and expand tumor-reactive T cells, targeting at least 10^9 cells with over 70% tumor-reactive T cells[100][98]. - The manufacturing strategy includes enhanced culture conditions to improve TIL quality and functional genetic modifications to sustain TIL activity post-infusion[75][76]. - The TIDAL-01 selection process has shown to enrich tumor-reactive T cells by approximately 30-fold compared to bulk TILs[106]. - Selected TILs showed a 3-fold increase in tumor-reactive CD4+ and CD8+ T cells compared to bulk TILs across 6 tumor samples[111]. Clinical Trials and Updates - Three ongoing Phase 1 clinical trials for TIDAL-01 include treatments for breast cancer, colorectal cancer, head and neck cancer, and uveal melanoma, with an initial clinical update expected in mid-2024[35]. - The ongoing Phase 1b clinical trial for the lead Selected TIL product candidate, TIDAL-01, aims to evaluate its effectiveness in solid tumors, including breast cancer and colorectal cancer[46]. - The clinical strategy includes a multicenter Phase 1 trial targeting 40 to 60 patients across breast cancer, colorectal cancer, head and neck cancer, and uveal melanoma[121]. - The primary endpoint of the trials will focus on safety and tolerability, with secondary endpoints assessing efficacy based on objective response rates and durability[129]. - Initial clinical updates across the trials are expected in mid-2024[129]. Manufacturing and Quality Control - TIDAL-02, the next Selected TIL program, is in preclinical development and aims to streamline manufacturing processes and enhance TIL quality[36]. - The manufacturing process for TIDAL-01 currently takes around eight weeks, with efforts underway to reduce this to approximately four weeks[99]. - TIDAL-02 aims to streamline manufacturing to less than three weeks and enhance TIL quality and function through direct selection and genetic modifications[130]. - The company has established partnerships with global CDMOs for bioprocess development and cGMP manufacturing, including a close collaboration with Moffitt Cancer Center for TIDAL-01[148]. Financial Overview - The company has raised a total of $449.8 million in capital, including $172.0 million from preferred stock financings and $190.0 million from non-dilutive payments from strategic partnerships, with an IPO raising $80.0 million completed on July 25, 2023[44]. - The company is obligated to pay the Myst Holders $3.0 million within 45 days of achieving the initial milestone, which was met on July 25, 2023[160]. - The second milestone, achieved in May 2022, required a total payment of $10.0 million, split equally between cash and shares, with $5.0 million paid in cash and $5.0 million in shares[161]. - The company is required to make tiered sales-based milestone payments to Moffitt of up to $50.0 million based on aggregate net sales of all TIL Products[173]. Market and Competitive Landscape - The market for immune checkpoint inhibitors (ICIs) reached approximately $40.0 billion in worldwide sales in 2022, but less than 15% of cancer patients respond to ICI therapy[49]. - The company faces competition from various biotechnology firms developing TIL therapies, including Iovance Biotherapeutics, which received FDA approval for the first TIL therapy[153]. - The company anticipates intense competition as new drugs and therapies enter the market, with competitors having greater financial and technical resources[152]. Regulatory Considerations - The FDA reviews a BLA within ten months for standard applications and six months for priority reviews after acceptance for filing[207]. - The BLA submission must include all relevant data from preclinical and clinical studies, including negative results[205]. - The manufacturing process must comply with cGMP requirements to ensure consistent production of the product[208]. - The FDA inspects manufacturing facilities and clinical sites before approving a BLA to ensure compliance with regulatory standards[208].