IDO-derived peptide vaccine/PD-L1-derived peptide vaccine(Herlev Hospital)

Dr. Zocca brings more than 20 years of experience in the biotechnology field and has founded and co-founded several biotech spinouts. Her focus on translational and clinical immune oncology has led to the development of important investigational immunotherapies for a variety of cancer types. Dr. Zocca holds a Ph.D. in tumor immunology and a Master of Science in biochemistry. She received her Ph.D. from the Institute of Medical Microbiology and Immunology, University of Copenhagen, and the NIH, National Cancer Institute (NCI), Bethesda, Maryland, USA.For many patients with advanced stage or rapidly progressing cancers, new treatments cant come fast enough. Current therapies for common cancers such as melanoma often force patients and their healthcare providers to choose between strong efficacy with potentially serious side effects, or moderate efficacy and moderate toxicity. Throughout my career in academia and industry, Ive been captivated by the potential of therapies that could help strip down the defenses used by cancer cells to keep the immune system at bay.Aiming to transform the lives of cancer patients by improving patient outcomes, I founded IO Biotech in 2014 to develop novel therapeutic vaccines that seek to alter the tumor microenvironment to make it hostile to cancer cells.Challenges with current approaches to cancer treatmentCancer has always been difficult to treat because it defends itself so effectively against the bodys immune system. Treatments that single out specific proteins that are overexpressed in the tumor microenvironment can target tumor cells directly while also enabling the bodys own immune defenses to attack and kill those cells more effectively on their own.However, tumor cells and other cells in the tumor microenvironment express proteins that block T cells from killing cancer cells. The advent of immune checkpoint inhibitors (ICIs) made cancer cells more vulnerable to T cells by disrupting the proteins that block immune response. Unfortunately, cancers resistance to these therapies can limit the efficacy of this approach. Finding ways to dismantle cancers escape mechanisms and counter that resistance could help improve the efficacy of cancer treatments.A promising approach to dismantling cancers defensesIn addition to targeting and destroying tumor cells themselves, cancer vaccines also have the potential to improve the mechanism that makes ICIs work by targeting the cells that generate immune system resistance. Some vaccines target neoantigensproteins with unique mutations expressed only by tumor cells. These vaccines are highly targeted, but they must be customized for each patient.Other vaccines are designed to activate T cell immunity against proteins commonly overexpressed by specific cancers. This approach may enable biotech companies to produce off-the-shelf therapies that can be manufactured more easily, delivered to patients more quickly, and applied more broadly across patient populations. These vaccines may also be able to target immune-suppressive antigens expressed by non-tumor cells in the tumor microenvironment, potentially improving the therapies efficacy. Targeting both tumor and non-tumor cells is intended to effectively jump-start the bodys immune response, activating it to help destroy both types of cells on its own. Ideally, the therapy transforms the tumor microenvironment from protective toward cancer cells to hostile to them.The latter approach shows considerable promise. At IO Biotech, our T-win platform leverages a catalog of molecules to generate off-the-shelf drug candidates targeting antigens that allow cancers to avoid attack by the bodys immune system. Our lead candidate, IO102-IO103, targets cells that produce IDO and PDL-1, two antigens commonly overexpressed in melanoma patients tumor microenvironments. A Phase 1/2 trial, which combined IO102-IO103 with nivolumab in metastatic melanoma, produced a high objective response rate (ORR) of 80%, with 50% of patients reaching a complete response and a median progression-free survival of nearly 26 months.1 Importantly, the overall safety and tolerability data were comparable to those of ICI therapies targeting the PD-1 antigen alone, with IO102-IO103 not adding any systemic toxicity.2 Results from an ongoing Phase 3 clinical trial could bring the therapy to patients in the United States as early as 2025.Whats next for cancer vaccinesTargeting antigens in the tumor microenvironment could deliver much-needed hope to patients beyond the growing population of people with melanoma. If IO102-IO103 clinical results continue to demonstrate the combination of safety and efficacy we have seen so far without adding systemic toxicity, it could provide another therapeutic option for melanoma patients. Provided we can identify the right antigens to target, this approach could also offer hope to patients with a variety of difficult-to-treat cancers. It also could have an impact in other therapeutic areas that have not benefited from new treatments in some time.Sources:1 Lorentzen et al, 20232 Kjeldsen et al, 2021 '

Outcome of interim analysis for the overall response rate (ORR) for the first 225 patients randomized in the pivotal Phase 3 trial (IOB-013/KN-D18) of lead investigational therapeutic cancer vaccine, IO102-IO103, in combination with pembrolizumab still expected in Q3 2024; outcome of primary endpoint of progression free survival (PFS) is now projected to occur in first half of 2025 Completed enrollment in Phase 2 basket trial IOB-022/KN-D38 and in first cohort of Phase 2 neoadjuvant/adjuvant basket trial IOB-032/PN-E40, which has been expanded to include a randomized melanoma cohort Presented poster at the American Association for Cancer Research (AACR) Annual Meeting 2024; non-clinical data presented further support the dual mechanism of action of IO102-IO103 Strengthened executive team with key hires to business and commercial development positions Ended first quarter with approximately $118.0 million in cash and cash equivalents, maintaining expected cash runway into the fourth quarter of 2025 NEW YORK, May 14, 2024 (GLOBE NEWSWIRE) -- IO Biotech (Nasdaq: IOBT), a clinical-stage biopharmaceutical company developing novel, immune-modulating therapeutic cancer vaccines based on its T-win® platform, today reported financial results for the first quarter ended March 31, 2024. “This will be a transformative year for IO Biotech as we approach the interim analysis of our pivotal Phase 3 study in first-line advanced melanoma, which, if supportive, could allow for a submission of a Biologics License Application (BLA) to the United States (US) Food and Drug Administration (FDA) this year,” said Mai-Britt Zocca, Ph.D., President and CEO of IO Biotech. “Last year, we expanded our Phase 3 study to potentially bring in the time to reach the primary endpoint of progression free survival and we concluded enrollment in the fourth quarter of 2023 with 407 patients. As we prepare for the interim analysis, we now have greater visibility to estimate the timing of reaching 226 events needed for the PFS analysis, which we now project will occur in the first half of 2025.” Dr. Zocca continued, “With continued execution of our Phase 3 study and its planned interim analysis as our main priorities this year, we also continue both of our Phase 2 basket studies: completing enrollment in our IOB-022 study; and rapidly enrolling and expanding our newest basket study, IOB-032, in the neo-adjuvant/adjuvant settings of melanoma and squamous cell carcinoma of the head and neck (SCCHN). Finally, as we prepare for potential commercialization and partnering, I am very pleased with the strength of expertise we have added to our leadership team with the additions of Marjan Shamsaei as Senior Vice President, Commercial and Portfolio Lead, and Faiçal Miyara as Chief Business Officer. I founded IO Biotech 10 years ago and couldn’t be more proud of all that we have accomplished, and, with such a strong team in place, confident in what lies ahead.” Recent Business Highlights The company recently completed enrollment of 407 patients in its pivotal Phase 3 trial (IOB-013/KN-D18) of IO102-IO103 in combination with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in advanced melanoma. The primary endpoint of the Phase 3 trial is PFS. The PFS analysis will be conducted when 226 events have occurred in the trial, which, based on the expanded trial size, reaching full enrollment ahead of schedule and the events to date in the study, the company now projects will occur in the first half of 2025. Additionally, a planned interim analysis of ORR will be conducted when the first 225 randomized patients reach one year of treatment in June 2024. The outcome of this analysis is expected in the third quarter of 2024 and, if supportive, we believe could allow for submission of a BLA for accelerated approval in the US. The independent data monitoring committee (IDMC) for the company’s IOB-013/KN-D18 Phase 3 trial convened its fourth meeting in March 2024 and recommended that the trial continue without modifications. The company’s Phase 2 basket trial (IOB-022/KN-D38) evaluating IO102-IO103 in combination with pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC) or recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) completed enrollment; the company plans to submit abstracts with updates from this study to medical meetings in the fall of 2024. The company’s Phase 2 solid tumor basket trial (IOB-032/PN-E40) studying treatment with IO102-IO103 in combination with pembrolizumab given before (neo-adjuvant) and after (adjuvant) surgery with curative intent in patients with resectable melanoma or SCCHN has been enrolling patients since December 2023 in cohorts A (melanoma) and B (SCCHN) in the US, European Union (EU) and Australia. Cohort A is now fully enrolled and the company recently expanded the study to include a randomized cohort C in melanoma, in which patients are randomized either to IO102-IO103 in combination with pembrolizumab or to pembrolizumab alone. In April, a poster presentation of new non-clinical data further supporting the dual mechanism of action of the company’s lead cancer vaccine, IO102-IO103, was delivered at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego, California. While further studies are needed to fully discern the relationship between IDO1+/PD-L1+ target populations within the TME and the impact of IDO1/PD-L1 targeted vaccination, we believe the data presented support the use of a dual antigen approach to reduce the immunosuppression and enhance anti-tumor effect. In April, the company strengthened its executive team with the appointments of Faiçal Miyara, Ph.D., as Chief Business Officer, and Marjan Shamsaei, Pharm.D., as Senior Vice President, Commercial and Portfolio Lead. First Quarter 2024 Financial Results Net loss for the three months ended March 31, 2024, was $19.5 million, compared to $17.0 million for the three months ended March 31, 2023. Research and development expenses were $14.3 million for the three months ended March 31, 2024, compared to $11.9 million for the three months ended March 31, 2023. The increase was primarily related to clinical trial-related activities for the company’s IO102-IO103 therapeutic cancer vaccine candidate, including the continued execution of the company’s pivotal Phase 3 clinical trial. The company recognized $0.6 million in research and development equity-based compensation for the three months ended March 31, 2024, compared to $0.7 million for the three months ended March 31, 2023. General and administrative expenses were $5.9 million for the three months ended March 31, 2024, compared to $6.0 million for the three months ended March 31, 2023. The company recognized $1.0 million in general and administrative equity-based compensation for the three months ended March 31, 2024, compared to $1.2 million for the three months ended March 31, 2023. Cash and cash equivalents as of March 31, 2024 were $118.0 million, compared to $143.2 million at December 31, 2023. During the three months ended March 31, 2024, the company used cash, cash equivalents and restricted cash of $24.9 million. The increase in cash use was primarily driven by milestone payments and payment of other accrued expenses associated with clinical trials, as well as the payment of year-end bonuses. The company continues to expect that it will have sufficient cash to run the company into the fourth quarter of 2025. About IO102-IO103 IO102-IO103 is an investigational off-the-shelf therapeutic cancer vaccine designed to kill both tumor cells and immune-suppressive cells in the tumor microenvironment (TME) by stimulating activation and expansion of T cells against indoleamine 2,3-dioxygenase (IDO) positive and programmed death-ligand 1 (PD-L1) positive cells. The company is currently conducting a pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) investigating IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with advanced melanoma, a Phase 2 basket trial (IOB-022/KN-D38; NCT05077709) investigating IO102-IO103 in combination with pembrolizumab as first line treatment in patients with solid tumors, and a Phase 2 basket trial (IOB-032/PN-E40; NCT05280314) investigating IO102-IO103 in combination with pembrolizumab as neo-adjuvant/adjuvant treatment of patients with solid tumors. The clinical trials are sponsored by IO Biotech and conducted in collaboration with Merck and Merck is supplying pembrolizumab. IO Biotech maintains global commercial rights to IO102-IO103. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About the IOB-013/KN-D18 Pivotal Phase 3 Clinical Trial IOB-013/KN-D18 (Clinical Trials.gov: NCT05155254) is an open label, randomized Phase 3 clinical trial of IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with previously untreated, unresectable or metastatic (advanced) melanoma, being conducted in collaboration with Merck. Patients have been enrolled from centers across the United States, Europe, Australia, Turkey, Israel and South Africa. The primary endpoint of the study is progression free survival. Biomarker analyses will also be conducted. IO Biotech is sponsoring the Phase 3 trial and Merck is supplying pembrolizumab. IO Biotech maintains global commercial rights to IO102-IO103. About the IOB-013/KN-D18 Clinical Trial Endpoints The primary endpoint of the IOB-013/KN-D18 trial is progression free survival (PFS). The PFS analysis is event-driven and will be conducted when 226 events have occurred in the trial, which the company estimates will take place in the first half of 2025. Additionally, there is a planned per-protocol interim analysis of overall response rate when the first 225 randomized patients reach one year of treatment in mid-2024. The outcome of this analysis is expected in the third quarter of 2024. There is a high statistical bar for the Phase 3 interim analysis (p≤0.005), which was set to preserve most of the alpha for the primary endpoint of PFS. Regardless of the outcome of the interim analysis, the trial is designed to continue to the primary PFS endpoint. About IOB-022/KN-D38 Phase 2 Solid Tumor Basket Trial IOB-022/KN-D38 (NCT05077709) is a non-comparative, open label trial to investigate the safety and efficacy of IO102-IO103 in combination with pembrolizumab in first-line advanced cancers in non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). IO Biotech is sponsoring the Phase 2 trial and Merck is supplying pembrolizumab. IO Biotech maintains global commercial rights to IO102-IO103. About IOB-032/PN-E40 Phase 2 Solid Tumor Basket Trial IOB-032/PN-E40 (NCT05280314) is a Phase 2 basket trial investigating the IO102-IO103 therapeutic cancer vaccine in combination with pembrolizumab as neo-adjuvant/adjuvant treatment of patients with solid tumors. The study will enroll approximately 15 patients with melanoma and 15 patients with SCCHN in cohort A and cohort B respectively as single arm cohorts receiving combination of IO102-IO103 with pembrolizumab, whereas in cohort C ≥30 melanoma patients will be randomized 1:1 to neo-adjuvant treatment with either the combination of IO102-IO103 with pembrolizumab or pembrolizumab alone. In the neo-adjuvant period, for all cohorts, treatment is every 3 weeks (Q3W) for 3 cycles (melanoma) or 2-3 cycles (SCCHN). Patients entering the study will be scheduled for surgery and begin neoadjuvant treatment 4-9 weeks prior. Surgery will be followed by adjuvant treatment with the same regimen for 15 cycles. Cohort C patients with poor pathological response to pembrolizumab alone in the neo-adjuvant phase (>10% residual viable tumor) may cross over to combination treatment post-surgery. The primary endpoint is major pathological response at surgery (≤10% residual viable tumor; central assessment). IO Biotech is sponsoring the Phase 2 trial and Merck is supplying pembrolizumab. About IO Biotech IO Biotech is a clinical-stage biopharmaceutical company developing novel, immune-modulating therapeutic cancer vaccines based on its T-win® platform. The T-win platform is based on a novel approach to cancer vaccines designed to activate T cells to target the immunosuppressive cells in the tumor microenvironment. IO Biotech is advancing its lead cancer vaccine candidate, IO102-IO103, in clinical trials, and additional pipeline candidates through preclinical development. Based on positive Phase 1/2 first line metastatic melanoma data, IO102-IO103, in combination with pembrolizumab, has been granted a breakthrough therapy designation for the treatment of advanced melanoma by the US Food and Drug Administration. IO Biotech is headquartered in Copenhagen, Denmark and has US headquarters in New York, New York. For further information, please visit . Follow us on our social media channels on LinkedIn and X (@IOBiotech). Forward-Looking Statement This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements, including regarding the timing of the interim and primary analyses of the company’s Phase 3 trial, current or future clinical trials, their progress, enrollment or results, or the company’s financial position or cash runway, are based on IO Biotech’s current assumptions and expectations of future events and trends, which affect or may affect its business, strategy, operations or financial performance, and actual results and other events may differ materially from those expressed or implied in such statements due to numerous risks and uncertainties. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Because forward-looking statements are inherently subject to risks and uncertainties, you should not rely on these forward-looking statements as predictions of future events. These forward-looking statements speak only as of the date hereof and should not be unduly relied upon. Except to the extent required by law, IO Biotech undertakes no obligation to update these statements, whether as a result of any new information, future developments or otherwise. Contact: Maryann Cimino, Director of Investor Relations IO Biotech, Inc. 617-710-7305 mci@iobiotech.com IO BIOTECH, INC. Consolidated Statements of Operations and Comprehensive Loss (Unaudited in thousands, except share and per share amounts) Three Months Ended March 31, 2024 2023 Operating expenses Research and development $ 14,311 $ 11,900 General and administrative 5,886 6,024 Total operating expenses 20,197 17,924 Loss from operations (20,197 ) (17,924 ) Other income (expense) Currency exchange (loss) gain, net (462 ) 258 Interest income 1,617 1,028 Total other income (expense) 1,155 1,286 Loss before income tax expense (19,042 ) (16,638 ) Income tax expense 415 406 Net loss (19,457 ) (17,044 ) Net loss attributable to common shareholders (19,457 ) (17,044 ) Net loss per common share, basic and diluted $ (0.30 ) $ (0.59 ) Weighted-average number of shares used in computing net loss per common share, basic and diluted 65,880,914 28,815,267 Other comprehensive loss Net loss $ (19,457 ) $ (17,044 ) Foreign currency translation 194 517 Total comprehensive loss $ (19,263 ) $ (16,527 ) IO BIOTECH, INC. Consolidated Balance Sheets (Unaudited in thousands, except share and per share amounts) March 31, 2024 December 31, 2023 Assets Current assets Cash and cash equivalents $ 117,982 $ 143,193 Prepaid expenses and other current assets 6,146 4,062 Total current assets 124,128 147,255 Restricted cash 268 268 Property and equipment, net 788 847 Right of use lease asset 2,092 2,259 Other non-current assets 883 89 Total non-current assets 4,031 3,463 Total assets $ 128,159 $ 150,718 Liabilities and stockholders’ equity Current liabilities Accounts payable $ 3,840 $ 3,878 Lease liability - current 666 655 Accrued expenses and other current liabilities 6,537 11,184 Total current liabilities 11,043 15,717 Lease liability - non-current 1,650 1,839 Total non-current liabilities 1,650 1,839 Total liabilities 12,693 17,556 Commitments and contingencies (Note 9) Stockholders’ equity Preferred stock, par value of $0.001 per share; 5,000,000 shares authorized, no shares issued and outstanding as of March 31, 2024 and December 31, 2023 — — Common stock, par value of $0.001 per share; 300,000,000 shares authorized at March 31, 2024 and December 31, 2023; 65,880,914 shares issued and outstanding as of March 31, 2024 and December 31, 2023, respectively 66 66 Additional paid-in capital 408,154 406,587 Accumulated deficit (283,279 ) (263,822 ) Accumulated other comprehensive loss (9,475 ) (9,669 ) Total stockholders’ equity 115,466 133,162 Total liabilities and stockholders’ equity $ 128,159 $ 150,718