UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
(Exact name of registrant as specified in its charter)
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
(Address of principal executive offices)
Registrant’s telephone number, including area code:
N/A
(Former name or former address, if changed since last report.)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading |
Name of each exchange | ||
Indicate by check mark whether the registrant is an emerging growth company as defined in as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Item 7.01 Regulation FD Disclosure.
On March 5, 2024, Turnstone Biologics Corp. (“Turnstone” or the “Company”) made available an updated corporate presentation that the Company will use to present at the TD Cowen 44th Annual Global Health Care Conference on March 6, 2024, which can be found on the Company’s website. A copy of the presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K and incorporated by reference into this Item 7.01.
The information provided in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1 hereto, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liability of that section, nor shall it be deemed incorporated by reference into any of the Company’s filings under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, regardless of any incorporation language in such a filing, except as expressly set forth by specific reference in such a filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
| Exhibit No. | Description | |
| 99.1 | Corporate Presentation (March 2024) | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| ACELYRIN, INC. | ||
| By: | /s/ Sammy Farah | |
| Sammy Farah, M.B.A., Ph.D. | ||
| President and Chief Executive Officer and Director | ||
Dated: March 5, 2024
Corporate Presentation March 2024 Nasdaq: TSBX Non-Confidential Exhibit 99.1
This presentation and any accompanying oral commentary have been prepared by Turnstone Biologics Corp. (“Turnstone”) for informational purposes only and not for any other purpose. All statements contained in this presentation and the accompanying oral commentary, other than statements of historical facts, are forward-looking statements, including: statements about our expectations regarding the potential benefits, activity, effectiveness, and safety of our Selected tumor-infiltrating lymphocyte (TIL) product candidates and programs; our expectations with regard to the design and results of our research and development programs, preclinical studies, and clinical trials, including the timing and availability of data from such trials; our preclinical, clinical, and regulatory development plans for our Selected TIL product candidates and programs, including the timing or likelihood of regulatory filings and approvals for our Selected TIL product candidates; our ability to maintain existing, and establish new, strategic collaborations, licensing, or other arrangements; our ability to improve process to improve manufacturing processes; and our business strategy. These statements involve substantial known and unknown risks, uncertainties and other factors that may cause our actual results, timing of results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. These risks and uncertainties include those factors discussed in the Quarterly Report on Form 10-Q filed with the U.S. Securities and Exchange Commission ("SEC") on November 13, 2023, under the heading “Risk Factors,” and other documents Turntone has filed, or will file, with the SEC. These filings, when available, are available on the investor relations section of our website at ir.turnstonebio.com and on the SEC’s website at www.sec.gov. New risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially and adversely from those anticipated or implied in the forward-looking statements. We may not actually achieve the plans, intentions, or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. The forward-looking statements in this presentation represent our views as of the date of this presentation. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. Except as required by law, none of Turnstone, its affiliates or any of their respective employees, directors, officers, contractors, advisors, members, successors, representatives or agents makes any representation or warranty as to the accuracy or completeness of any information contained in this presentation and shall have no liability for any representations (expressed or implied) contained in, or for any omissions from, this presentation. This presentation contains trademarks, service marks, trade names and copyrights of Turnstone and other companies which are the property of their respective owners. This presentation discusses product candidates that are under clinical study and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these product candidates for the uses for which they are being studied. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Disclaimers
Turnstone is Pioneering Advancements in Selected TIL Therapy Next-Generation Therapy Designed to Treat and Cure Solid Tumors OUR MISSION Profoundly transform the treatment paradigm for patients with a broad range of solid tumors with next-generation TIL therapies that overcome the limitations of current treatment options Mike Mielnik Senior Scientist, Turnstone Biologics
Solid Tumors Represent a Serious Unmet Medical Need Approximately 90% of all new cancers per year are solid tumors 1National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER), accessed March 2024; 2Cancer Metastasis: Guan X. Cancer Metastases: Challenges and Opportunities. Acta Pharm Sin B. 2015 Sep;5(5):402-18.; 3Haslam A, Prasad V. Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs. JAMA Netw Open. 2019 May 3;2(5):e192535.; 4United Stated Food and Drug Association (US FDA) approval granted on 02/16/2024; News release Checkpoint inhibitors only benefit a fraction of cancer patients3 Targeted and other cell therapies have shown only limited success One FDA approved TIL therapy and only in advanced melanoma4 1.6M 500K 90%+ new cancer patients1 deaths with low long-term survival1 mortality in metastatic disease2 In the U.S. Each Year New Therapeutic Options Urgently Needed
Indication Spotlight: Colorectal Cancer (CRC) 2nd Leading Cause of U.S. Cancer Deaths1 3rd 153K 53K most commonly diagnosed cancer2 expected new cases this year3 number of deaths expected in 20244 Difficult-To-Treat Tumor Unresponsive To Most Immune-Based Therapies Immunologically “cold” tumor characterized by low tumor mutational burden (TMB) Turnstone is Tackling Solid Tumors of Greatest Need Our focus is on colorectal cancer, head and neck cancer, uveal melanoma and breast cancer We believe the key to overcoming challenges of CRC and other “cold” tumors is large numbers of on-target tumor-reactive T cells which is the foundation for Turnstone’s approach of Selected TIL therapy 2CA: A Cancer Journal for Clinicians – Colorectal Cancer Statistics, 2023 – DOI: 10.3322/caac.21772; 3, 4National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER), accessed March 2024 1American Cancer Society. Cancer Facts & Figures 2024; 2nd
Turnstone is Pioneering Advancements in Selected TIL Therapy Next-generation therapy designed to treat and cure solid tumors Differentiated approach centered around tumor-reactive T cell selection (Selected TILs) Lead asset, TIDAL-01, being evaluated in multiple Phase 1 studies with initial clinical data expected in mid-2024 Targeting underserved solid tumor patient populations, including CRC, HNSCC, uveal melanoma and breast cancer TILs have been recently approved by the FDA* for the treatment of cutaneous melanoma FDA = United States Food and Drug Administration; CRC = Colorectal cancer; HNSCC = Head and neck squamous cell carcinoma *Approval for Amtagvi granted on 02/16/2024; US FDA news release
Sammy Farah, MBA, PhD Chief Executive Officer Vijay Chiruvolu, MBA, PhD Interim Chief Technology Officer Venkat Ramanan, PhD Chief Financial Officer Stewart Abbot, PhD Chief Scientific Officer Saryah Azmat Chief Business Officer Mike Burgess, MBChB, PhD Interim Chief Medical Officer 20+ years of scientific, business and executive management experience in biotech industry Held senior positions at Merck, Immune Design, and Synthetic Genomics Previously at Versant Ventures specializing in biotechnology investing and new company formation 10+ years of experience in biopharma business development, corporate strategy and capital formation Former Global Lead for Oncology Search & Evaluation at Bristol-Myers Squibb, executing over 15 major transactions from preclinical to clinical development 27+ years of manufacturing and process development experience Served as SVP of Global Process Development-Cell Therapy at Kite Pharma/Gilead Sciences, responsible for the CMC/process development leading to regulatory approval of two cell therapy products, Yescarta and Tecartus 20+ years of biopharma finance and operations experience Joined from Seagen where he led the Finance function as the company launched several products, expanded global footprint and executed multiple strategic transactions 20+ years experience building and leading clinical development Led strategy and execution of translational medicine across all therapeutic areas as SVP of Cardiovascular, Fibrosis and Immunoscience Development at Bristol-Myers Squibb Previous Global Head of Oncology Research and Early Development at Roche 20+ years of R&D experience in cell-based and immuno-oncology products Former CSO and COO at Adicet Bio, responsible for R&D activities for allogeneic gamma delta T cell therapies Previously CDO at Fate Therapeutics, developing cellular immunotherapies Turnstone Executive Team Proven experience across all areas and stages of drug development
Distinguished Advisors Key Collaborators Simon Turcotte, MD, MSc Associate Professor of Surgery; Lead of Adoptive T Cell Cancer Immunotherapy Program, University of Montreal Hospital Research Centre (CRCHUM) James Mulé, PhD Associate Center Director of Translational Science Moffitt Cancer Center Steven A. Rosenberg, MD, PhD Chief of Surgery Branch National Cancer Institute Malcolm Brenner, MD, PhD Professor, Center for Cell and Gene Therapy Baylor College of Medicine Thomas Dubensky Jr., PhD Founder and Advisor Tempest Therapeutics Bernard Fox, PhD Chief, Laboratory of Molecular and Tumor Immunology Providence Cancer Institute Adrian Hill, PhD Director, The Jenner Institute University of Oxford Robert Seder, MD Chief, Cellular Immunology Section Vaccine Research Center National Institutes of Health Alan Melcher, PhD Team Leader Translational Immunology The Institute of Cancer Research Nicholas Restifo, MD Special Volunteer National Institutes of Health Eric Tran, PhD ACT Laboratory Lead Providence Cancer Institute Jeffrey S. Weber, MD, PhD Deputy Director, PCC; Co-Director, Melanoma Research Program NYU-Langone Cancer Center Turnstone External Network Supported by prominent scientific and corporate advisors and collaborators Tassos Gianakakos, MBA Former CEO MyoKardia
Turnstone Pipeline Opportunity to address broad set of solid tumor patient populations Product Overview Program Key Indications Preclinical Phase 1 Phase 2 Phase 3 Next Anticipated Milestone Selected TILs TIDAL-01 TIDAL-02 Initial clinical data in mid-2024 IND submission IND submission Tumor-reactive Selected TILs Combination with viral immunotherapy Selected TILs with next-gen manufacturing and TIL quality enhancements Solid tumors Solid tumors Colorectal cancer, Head and neck cancer, Cutaneous and non-cutaneous melanomas Breast cancer, Colorectal cancer, Head and neck cancer, Uveal melanoma *Investigator sponsored trials at Moffitt Cancer Center Moffitt Collaboration*
SELECTED TILs AND TIDAL-01 Corporate Presentation | March 2024
Expanding the Frontiers of TIL Therapy Building upon first-to-market TIL therapy to deliver differentiated product with unique market opportunity Turnstone is developing the Next-Generation of TIL Therapies First approval for a TIL therapy brings new option for solid tumors Amtagvi is the first and only FDA-approved TIL therapy, and the only T cell therapy for a solid tumor Amtagvi is a first-generation bulk TIL therapy approved to treat only advanced melanoma* Increasing total number of tumor-reactive T cells is key area of differentiation Academic studies provide early clinical evidence for selected TIL approach Potential to broaden efficacy into additional solid tumors with critical unmet need Bulk TILs have failed to show success in most solid tumors outside melanoma Significant opportunity for next-gen products More targeted and potent tumor killing is a must *Approval for Amtagvi granted on 02/16/2024; US FDA news release
Next-generation TIL therapy based on isolation, selection and expansion of tumor-reactive T cells to improve product potency¹ Designed to address a broad range of solid tumor types Selected TILs Selected TILs Have Potential for More Targeted Tumor Killing Starting materials for solid tumors typically have small number and proportion of tumor-reactive T cells Solid Tumors Tumor-reactive T cells can contribute to tumor killing Bulk TILs: Non-specific expansion of all cells Selected TILs: Specific expansion of tumor-reactive T cells 109+ cells with low number and proportion (reported median < 3%) of on target tumor-reactive T cells Large number and proportion of suppressive bystander cells Inefficient tumor killing observed to date 109+ cells with large number and proportion (targeting > 70%) of on-target tumor-reactive T cells Low number and proportion of suppressive bystander cells Potential for targeted tumor killing Tumor-Reactive T Cells Suppressive Bystander Cells 1 We define potency as the specific ability or capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through the administration of the product in the manner intended, to effect a given result
Early academics working on first-generation TILs led to development of a leading Bulk TIL company’s current process Success to date has been limited to melanoma Bulk TILs Melanoma Sheba, NCI, Moffitt, MD Anderson Melanoma Bulk TIL leading competitor clinical development initiation Cervical NCI Melanoma and Cervical Competitor Data Release Head and Neck Cancer Competitor Data Release Melanoma Competitor Data Release Selected TILs Bile Duct Tran et. al (NCI) Colorectal Cancer Tran et. al (NCI) Breast Cancer, Colorectal Cancer, Head and Neck Cancer, Uveal Melanoma** Breast Zacharakis et al (NCI) Lung Creelan et. al (Moffitt) Selected TILs Are Based on Advances from Academia Melanoma Rosenberg et. al, NCI Melanoma First FDA approval for TIL therapy (Amtagvi)* *Approval for Amtagvi granted on 02/16/2024; US FDA news release; **Indications being evaluated in ongoing Phase 1 studies Recent academic data in next-generation TILs has provided early clinical evidence for next-generation selected TIL approach Objective responses extended to other major solid tumor types
*7 patients received TIL product with confirmed tumor-specific reactivity out of 13 patients who were evaluable for clinical response †6 patients enrolled on adoptive cell transfer protocol of enriched neoantigen-specific TIL out of 28 patients who contained TIL that recognized at least one immunogenic somatic mutation 1 Early academic selection and enrichment strategies typically utilized fragment-based selection and expansion approaches. Following harvest and dissection of the tumor, small numbers of tumor fragments were placed into separate multi-well tissue culture dishes and cultured with the tumor or manufactured antigens. TIL populations that were activated by exposure to tumor antigens in culture would then be identified based on cytokine expression and/or T cell activation marker expression, and only those activated TIL populations would be expanded for use in the final product Tumor Type N Response Source Academic Selected TILs Bile Duct (Cholangiocarcinoma) 1 1 PR NCI - Tran et al; Science 2014 Colorectal Cancer 1 1 PR NCI - Tran et al; NEJM 2016 Non-Small Cell Lung Cancer 7* 2 CRs, 1PR Moffitt - Creelan et al; Nature Medicine 2021 Breast Cancer 6† 1 CR, 2 PRs NCI - Zacharakis et al; JCO 2022 Early academic selection strategies1 deployed at the NCI have demonstrated clinical POC Historical data from the NCI demonstrates limited evidence of benefit of Bulk TILs in epithelial malignancies Tumor Type N Response Source Bulk TILs Various Solid Tumors (including Colorectal, Bile Duct, Pancreas, Breast, Gastric) 50+ No success NCI – Rosenberg AACR 2020 / NCT01585428 Clinical Validation of Selected TILs
Tumor sequencing to identify all possible tumor mutations (antigens) Synthesize the tumor mutations in the form of long peptides Pulse patient-derived dendritic cells with the synthesized tumor antigens for natural processing and presentation Incubate TILs with presented tumor antigens and select tumor-reactive T cells based on activation markers TIDAL-01 Process Designed to select a more potent population of T cells The TIDAL-01 process is similar to standard bulk TIL processes but includes a selection step designed to create a TIL product with a significantly higher proportion of tumor-reactive T cells for more effective tumor killing Standard TIL Process TIDAL-01 Selected TILs Tumor Harvest TIL Isolation TIL Expansion Bulk TILs Product Infusion Tumor Harvest TIL Isolation TIL Expansion Selected TILs Product Infusion Key Selection Steps TIL SELECTION
TIDAL-01 product consists of diverse set of T cells with confirmed tumor-reactivity (TCRs) Selected tumor-reactive T cells are typically found in only very low frequencies in Bulk TILs These TCRs within Selected TILs deliver higher frequency of immunostimulatory cytokine expression in CD4+ and CD8+ T cells vs. Bulk TILs CD4+ T cells CD8+ T cells TIDAL-01 Designed to Select for Tumor-Reactive T Cells that are Typically Only Found in Very Low Levels in Bulk TILs TIDAL-01 Selected TILs TIDAL-01 Selected TILs TCR Analyses IFNg Expression Analyses Selection of tumor-reactive TIL enriches TCR repertoire 31% of TIDAL-01 selected CD8+ T cells reacted to peptides compared to 3% in Bulk TIL, representing approx. a 10-fold increase 26% of TIDAL-01 selected CD4+ T cells reacted to peptides compared to 10% in Bulk TIL, representing approx. a 2.6-fold increase The top 12 enriched TCRs represent 60% of the TIDAL-01 final product while these same TCRs represent less than 2% of the bulk TILs and bystander cells Colorectal Cancer Patient Sample % TCR Frequency % of Final Product % IFNg + of CD8+ Cells % IFNg + of CD4+ Cells Bulk TILs Bystander Cells Bulk TILs Bystander Cells TIL + Unloaded APC TIL + Peptide Loaded APC TIL + Unloaded APC TIL + Peptide Loaded APC TIDAL-01 Selected TILs Bulk TILs Bystander Cells **** = p < 0.0001
TIDAL-01 Displays Higher Capacity to Kill Tumor Cells Melanoma Patient Sample Time: 0 Time: 2 Days TIDAL-01 Selected TILs Bystander Cells Tumor Only Effector to target ratio: 1:2 Tumor Cells T Cells Dead Cells (CAS3/7)
TIDAL-01 CLINICAL DEVELOPMENT Corporate Presentation | March 2024
TIDAL-01 Phase 1 Clinical Trials in Advanced Solid Tumors Demonstrate the safety, biology, initial efficacy and manufacturing feasibility of TIDAL-01 in a Phase 1, first-in-human, non-randomized, open-label, single-dose study in patients with advanced solid tumors Objective Structure Turnstone sponsored trial (STARLING) enrolling across 10+ clinical sites Two investigator sponsored trials (ISTs) in collaboration with Moffitt Cancer Center Colorectal cancer (CRC) Head and neck cancer (HNSCC) Uveal melanoma Breast cancer Colorectal cancer (CRC) Head and neck cancer (HNSCC) Uveal melanoma Cutaneous melanoma
TIDAL-01 Phase 1 Study is Actively Enrolling Patients Phase 1 Study Design TIL Manufacturing IL-2 ± a-PD-1* TIDAL-01 TIL Lymphodepletion Cy-Flu TIL Harvest & Apheresis *a-PD1 combination in STARLING clinical trial and in HNSCC and CRC under Moffitt ISTs; Patients will also be receiving pembrolizumab as their anti-PD-(L)1 treatment two weeks after the TIDAL-01 infusion. Pembrolizumab will be dosed every three weeks until confirmed progressive disease or CR TIDAL-01 TIL viable cells: ≥ 1x109 High dose IL-2 (consistent with Bulk TIL doses) Study Objectives Primary Objective: Safety and tolerability Key Secondary Objectives: Overall response rate (ORR) Duration of response (DoR) We intend to provide an initial clinical update across our trials in mid-2024
TIDAL-01 Phase 1 Indication Focus on Multiple Solid Tumors with Critical Unmet Need With approximately 539K new cases1 and 107K deaths2 in the U.S. annually, Turnstone is targeting indications with serious disease burdens Multiple high-value targets allow for exploration with FIH therapy (some of which are supported by prior academic studies with selected TILs) Selected TIL therapies enriched for tumor-reactive T cells have the potential to drive efficacy in both low and high TMB solid tumors Turnstone intends to demonstrate the benefit of TIDAL-01 in solid tumors where objective response and/or durability of bulk TILs has not been established CRC = Colorectal cancer; HNSCC = Head and neck squamous cell carcinoma; FIH = First-in-human; TMB = Tumor-mutational burden U.S. New Cases U.S. 5-Year Survival3 New Cases and 5-yr Survival at Metastatic Diagnosis 1American Cancer Society. Cancer Facts & Figures 2024; National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER), accessed March 2024; Melanoma Research Alliance; Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71:7–33; ²American Cancer Society. Cancer Facts & Figures 2024; Barsouk A, Aluru JS, Rawla P, Saginala K, Barsouk A. Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med Sci (Basel). 2023 Jun 13;11(2):42. doi: 10.3390/medsci11020042. PMID: 37367741; PMCID: PMC10304137.; ³ Wang J, Li S, Liu Y, Zhang C, Li H, Lai B. Metastatic patterns and survival outcomes in patients with stage IV colon cancer: A population-based analysis. Cancer Med. 2020 Jan;9(1):361-373. doi: 10.1002/cam4.2673. Epub 2019 Nov 6. PMID: 31693304; PMCID: PMC6943094.; Barsouk A, Aluru JS, Rawla P, Saginala K, Barsouk A. Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med Sci (Basel). 2023 Jun 13;11(2):42. doi: 10.3390/medsci11020042. PMID: 37367741; PMCID: PMC10304137; Cancer.net - Breast Cancer - Metastatic: Statistics; Cancer.net – Eye Melanoma: Statistics
1NCCN Guidelines Version 4.2023; BRAFTOVI Prescribing Information; Erbitux Prescribing Information; Daiichi-Sankyo Press Release Aug 2023 (Enhertu BTD); JCO 40, 119-119(2022) (DESTINY-CRC01), Ann Surg Oncol. 2008 Sep;15(9):2388-94; Cancer Med. 2020 Feb; 9(3): 1044–1057; Onco Targets Ther. 2020 Dec 8:13:12601-12613; Cureus. 2023 Jan; 15(1): e33736. Clin Adv Hematol Oncol. 2018 Nov; 16(11): 735–745; Front Oncol. 2022; 12: 888181; JCO Precis Oncol. 2023 Jan:7:e2200179; Cancers (Basel). 2023 Feb; 15(4): 1022; Cancers (Basel). 2023 Apr; 15(8): 2288; 1L Nivo Plus Ipi Shows Benefit in mCRC; ²Dana Farber Cancer Institute; ³Ding K, Mou P, Wang Z, Liu S, Liu J, Lu H and Yu G (2023) The next bastion to be conquered in immunotherapy: microsatellite stable colorectal cancer. Front. Immunol. 14:1298524. doi: 10.3389/fimmu.2023.1298524 Indication Spotlight: Colorectal Cancer Our Phase 1 study is enrolling across all subtypes of 2nd and 3rd line CRC 1st and 2nd line options mainly limited to chemotherapy (FOLFIRI / FOLFOX) with or without targeted agent combinations (bevacizumab and/or anti-EGFR)¹ 3rd line treatment options are mostly targeted therapies with applicability limited to a small percentage of patients with specific mutations (i.e. BRAF-V600E, HER2)¹ No approved immunotherapies for MSS-CRC² which comprise 85% of all CRC cases³ 2nd and 3rd line agent ORRs range from 2-38% with supporting OS ranging from 7.4 – 14.5 months¹ Large patient numbers create significant market opportunity for Turnstone in 2nd and 3rd line metastatic CRC Metastatic CRC patients have very limited treatment options Treatments options for metastatic CRC are characterized by poor objective responses and low durability Unmet need remains high and market size is significant
Manufacturing Highlights Moffitt Cell Therapy Facility to support investigator sponsored trials and Charles River Laboratories to support the STARLING trial Turnstone intends to demonstrate the benefit of TIDAL-01 in solid tumors where objective response and/or durability of Bulk TILs has not been established Our primary focus for Phase 1 development is to demonstrate a consistent and reproducible TIDAL-01 product with target dose numbers in our desired indications Fully operational TIL therapy process and analytical development at our San Diego facility Our Current Focus Areas of Future Growth Internal Capabilities Two External cGMP Manufacturers for TIDAL-01 Manufacturing Time: We are optimizing the overall manufacturing time towards our target of 4 weeks and expect that all steps will be implemented prior to start of pivotal trials In-House Manufacturing: We are designing and intend to develop a fully integrated commercial manufacturing supply chain once clinical success of TIDAL-01 is demonstrated Moffitt = Moffitt Cancer Center
EMERGING PORTFOLIO AND COMPETITIVE PROFILE Corporate Presentation | March 2024
Emerging Pipeline with Significant Upside Potential Selected TILs + Virus TIDAL-02 Selected TILs with next-generation manufacturing and TIL functional and quality enhancements Viral immunotherapy pre-treatment and post- treatment in combination with TIDAL-01 Turnstone is building a TIL pipeline to further broaden objective responses and treat patients in earlier lines of therapy Direct Selection Enhanced Isolation and Expansion Gene Editing Proprietary combination of selection markers on tumor-reactive T cells to enable physical sort of reactive vs. bystander cells Culture media supplements added to improve and maintain TIL quality and function¹ ¹ TIL quality and function” means the viability of the TILs and their ability to produce cytotoxic and immune activating cytokines Gene edits designed to minimize dependance on exogenous IL-2 and resist exhaustion post infusion Drive a more diverse population of tumor-reactive T cells and increase T cell trafficking to tumor for superior quality and quantity of TIL harvest Pre-treatment: Expand access to indications less amenable to TIL therapy by optimizing TIL extraction Reprogram the immunosuppressive tumor microenvironment (e.g., turn a “cold” tumor “hot”) potentiating TIL infiltration, function, and proliferation within the tumor Post-treatment: Reprogram tumor with viral immunotherapy to improve the objective response of TIL treatment
Standard Bulk TILs Modified Bulk TILs Bulk TILs + Genetic Engineering Bulk TILs + Neoantigen Enrichment Bulk TILs + Culture Enhancements Turnstone Competitive Positioning Isolation and expansion of all TILs in the tumor Selected TILs Turnstone is pioneering advancements in Selected TIL Therapy Turnstone is making further modifications to the optimal population of Selected TILs Genetic Engineering Virus Combinations Culture Enhancements
Turnstone Biologics Highlights Initial clinical update from Phase 1 TIDAL-01 studies anticipated in mid-2024 TILs have been recently approved by the FDA for the treatment of cutaneous melanoma Academic studies provide early clinical evidence for next-generation selected TIL approach in multiple solid tumors Turnstone is developing Selected TILs to broaden potential treatment across the majority of solid tumors We are currently evaluating TIDAL-01 in multiple Phase 1 clinical trials focused on CRC, HNSCC, uveal melanoma, breast cancer and cutaneous melanoma
Non-Confidential Thank You