Mesenchymal Cell Neoplasm

U.S. FDA accepted BLA for afami-cel for the treatment of advanced synovial sarcoma with priority review and a PDUFA date of August 4th, 2024 Confirmatory evidence for afami-cel full approval agreed with FDA; will use data from Cohort 2 of pivotal SPEARHEAD-1 trial, which is fully enrolled Company is targeting launch of afami-cel upon receipt of FDA approval with commercial, manufacturing, and supply chain teams preparing for product delivery Lete-cel program transitioned back to Adaptimmune and the Company is planning for US commercial launch in 2026 Sarcoma franchise of afami-cel and lete-cel leverages same development and commercial footprint with US peak year sales projected to be up to $400 million Cash runway into early 2026; with greater than $300 million including current cash on hand, future expected income from partners and projected other non-dilutive capital sources Webcast to be held today, March 6, 2024, at 8:00 a.m. EST. (1:00 p.m. GMT) Company will hold an investor day at its Navy Yard facility on April 18th – more details to follow Philadelphia, Pennsylvania and Oxford, United Kindgom--(News - March 6, 2024) - Adaptimmune Therapeutics plc (NASDAQ: ADAP), a company redefining the treatment of solid tumor cancers with cell therapy, today reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a business update on the progress made in establishing its sarcoma franchise. Adrian Rawcliffe, Adaptimmune's Chief Executive Officer: "Adaptimmune is poised to bring afami-cel to market – which will be the first ever engineered T-cell therapy for a solid tumor. Afami-cel is the first product in our sarcoma franchise, which, if approved, along with lete-cel, has the potential to redefine the landscape for the treatment of advanced synovial sarcoma and MRCLS. This franchise, which is only the beginning of our commercial ambitions, is projected to deliver up to $400 million in U.S. peak year sales." Sarcoma Franchise Afami-cel Adaptimmune is preparing to launch the first product in its sarcoma franchise, afami-cel, for the treatment of advanced synovial sarcoma pending review and approval by the FDA with a PDUFA date of August 4, 2024. Synovial sarcoma is a solid tumor cancer with high unmet medical need for which there has been no new effective treatment since 2013. Synovial sarcoma represents 5%-10% of the ~13,000 soft tissue sarcoma cases in the United States each year.a If approved, afami-cel would be the first engineered T-cell therapy for a solid tumor to receive commercial approval in the U.S. Data from Cohort 2 of the pivotal trial SPEARHEAD-1 will serve as confirmatory evidence for full approval. This cohort is fully enrolled. Adaptimmune does not anticipate an advisory committee meeting, at this time, based on feedback received from FDA. Adaptimmune is preparing to launch afami-cel in Q3 of 2024 in the U.S. Initially, launch will be focused on 6-10 selected treatment centers ("Authorized Treatment Centers" or "ATCs") and will expand to up to ~30 additional ATCs. Field teams are being recruited and are engaging with ATCs. The marketing application for the companion diagnostic for MAGE-A4 is currently under FDA review and is expected to be approved contemporaneously with the BLA. Adaptimmune is a fully integrated cell therapy company and will deliver afami-cel's commercial supply from the Company's Navy Yard cell therapy manufacturing facility in Philadelphia. Adaptimmune's manufacturing and supply chain organization has delivered hundreds of clinical cell therapy batches to people enrolled in the Company's clinical trials, to date. Lete-cel The second product in Adaptimmune's sarcoma franchise, lete-cel, is being investigated in the pivotal IGNYTE-ESO trial (NCT03967223), which at an interim analysis exhibited response in 18/45 of patients (ORR 40%). The primary efficacy endpoint requires 16/60 patients have responses, so this trial has met its primary endpoint for efficacy. The full pivotal analyses are anticipated in late 2024. Adaptimmune has received an upfront amount and will receive milestone-based payments totaling £30 million under the agreement with GSK. Lete-cel will enable Adaptimmune to expand its addressable synovial sarcoma patient population by targeting the NY-ESO cancer antigen, in addition to MAGE-A4 targeted by afami-cel, as well as treating Myxoid Round Cell Liposarcoma (MRCLS) patients. Once approved and marketed, afami-cel and lete-cel have the potential to treat more than 1,000 people with soft tissue sarcomas annually in the United Statesb Clinical pipeline update As reported in ESMO 2023, ADP-A2M4CD8, Adaptimmune's next-generation engineered T-cell therapy exhibited 35% response rate in a broad range of solid tumors; 50% response rate in 26 patients with ovarian, urothelial, and head & neck cancers. ADP-A2M4CD8 is being investigated in the SURPASS-3 Phase 2 clinical trial (NCT05601752) for the treatment of platinum-resistant ovarian cancer. ADP-A2M4CD8 received FDA RMAT designation in 2022 for the treatment of patients with platinum resistant ovarian cancer. The SURPASS-3 trial is currently enrolling patients. Cohorts in the Phase 1 SURPASS trial are ongoing for people with head & neck and urothelial (bladder) cancers with ADP-A2M4CD8 in combination with standard of care checkpoint inhibitor therapy. Preclinical pipeline update IND-enabling studies are underway for ADP-600 (PRAME) and ADP-520 (CD70) programs Genentech collaboration to research and develop allogeneic cell therapies continues as planned Wholly owned allogeneic pipeline advancing; process development in progress at Adaptimmune's allogeneic manufacturing facility in Milton Park, UK. Corporate and other news Strategic combination with TCR2 Therapeutics completed in June of 2023 Cintia Piccina appointed as Chief Commercial Officer The Company received R&D tax credits from the UK government in January 2024 of $30.8m Financial Results for the three months and year ended December 31, 2023 Cash / liquidity position: As of December 31, 2023, Adaptimmune had cash and cash equivalents of $143.9 million and Total Liquidity1 of $146.9 million, compared to $108.0 million and $204.6 million, respectively, as of December 31, 2022. Revenue: Revenue for the three months and year ended December 31, 2023, was $0.2 million and $60.3 million, respectively, compared to $11.0 million and $27.1 million for the same periods in 2022. Revenue has increased in 2023, compared to the same period in 2022 primarily due to the termination of the Astellas collaboration, resulting in the remaining deferred income for the collaboration being recognized as revenue in March 2023. Research and development (R&D) expenses: R&D expenses for the three months and year ended December 31, 2023, were $33.2 million and $126.5 million, respectively, compared to $23.1 million and $127.7 million for the same periods in 2022. R&D expenses in the three months ended December 31, 2023 increased due to a decrease in offsetting reimbursements receivable for research and development tax and expenditure credits. R&D expenses in the year ended December 31, 2023 decreased due to a decrease in the average number of employees engaged in research and development following the restructuring completed in the first quarter of 2023, decreases in subcontracted expenditures, a decrease in share-based compensation expenses and a decrease in in-process research and development costs, which was mostly offset by a decrease in offsetting reimbursements receivable for research and development tax and expenditure credits. General and administrative (G&A) expenses: G&A expenses for the three months and year ended December 31, 2023, were $16.9 million and $73.5 million, respectively, compared to $15.2 million and $63.4 million for the same periods in 2022. G&A expenses in the year ended December 31, 2023 increased due to restructuring and charges recognised in the first quarter of 2023, an increase in other corporate costs due to an increase in accounting, legal and professional fees incurred in relation to the TCR2 Therapeutics, Inc merger agreement and severance and other related costs for former TCR2 Therapeutics leadership, offset by a decrease in share-based compensation expenses. Gain on bargain purchase: a $22.0 million gain on bargain purchase was recognised in the year ended December 31, 2023, from the strategic combination with TCR2 Therapeutics, Inc. Net loss: Net loss attributable to holders of the Company's ordinary shares for the three months and year ended December 31, 2023, was $47.9 million and $113.9 million, respectively ($(0.04) and $(0.09) per ordinary share), compared to $29.3 million and $165.5 million, respectively ($(0.03) and $(0.17) per ordinary share), for the same periods in 2022. Financial Guidance The Company believes that its existing cash, cash equivalents and marketable securities, together with the additional payments under the Strategic Collaboration and License Agreement with Genentech and payments under the Termination and Transfer Agreement with GSK, will fund the Company's current operations into early 2026, as further detailed in the Company's Annual Report on Form 10-K for the year ended December 31, 2023, to be filed with the Securities and Exchange Commission following this earnings release. Webcast Information The Company will host a live webcast to provide additional details at 8:00 a.m. EST (1:00 p.m. GMT) today, March 6, 2024. A live webcast of the conference call and replay can be accessed at . Call in information is as follows: 1-800-319-4610 (US or Canada) or +1-416-915-3239 (International and additional options available HERE). About Adaptimmune Adaptimmune is a clinical-stage biopharmaceutical company focused on designing, developing, and delivering cell therapies to transform the lives of people with cancer. The Company's unique engineered T-cell receptor (TCR) platform enables the engineering of T-cells to target and destroy cancers across multiple solid tumor types. Forward-Looking Statements This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA). These forward-looking statements involve certain risks and uncertainties. Such risks and uncertainties could cause our actual results to differ materially from those indicated by such forward-looking statements, and include, without limitation: the success, cost and timing of our product development activities and clinical trials and our ability to successfully advance our TCR therapeutic candidates through the regulatory and commercialization processes. For a further description of the risks and uncertainties that could cause our actual results to differ materially from those expressed in these forward-looking statements, as well as risks relating to our business in general, we refer you to our Annual Report on Form 10-K filed with the Securities and Exchange Commission for the year ended December 31, 2022, our Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and other filings with the Securities and Exchange Commission. The forward-looking statements contained in this press release speak only as of the date the statements were made and we do not undertake any obligation to update such forward-looking statements to reflect subsequent events or circumstances. Total Liquidity (a non-GAAP financial measure) Total Liquidity (a non-GAAP financial measure) is the total of cash and cash equivalents and marketable securities (available-for-sale debt securities). Each of these components appears separately in the condensed consolidated balance sheet. The U.S. GAAP financial measure most directly comparable to Total Liquidity is cash and cash equivalents as reported in the condensed consolidated financial statements, which reconciles to Total Liquidity as follows (in thousands): December 31, December 31, 2023 2022 Cash and cash equivalents $ 143,991 $ 108,033 Marketable securities - available-for-sale debt securities 2,947 96,572 Total Liquidity $ 146,938 $ 204,605 The Company believes that the presentation of Total Liquidity provides useful information to investors because management reviews Total Liquidity as part of its assessment of overall solvency and liquidity, financial flexibility, capital position and leverage. Condensed Consolidated Statement of Operations (unaudited, in thousands, except per share data) Three months ended Year ended December 31, December 31, 2023 2022 2023 2022 Development revenue 231 11,028 60,281 27,148 Revenue $ 231 $ 11,028 $ 60,281 $ 27,148 Research and development (33,208 ) (23,052 ) (126,509 ) (127,726 ) General and administrative (16,879 ) (15,218 ) (73,513 ) (63,387 ) Total operating expenses (50,087 ) (38,270 ) (200,022 ) (191,113 ) Operating loss (49,856 ) (27,242 ) (139,741 ) (163,965 ) Interest income 1,596 523 5,964 1,542 Gain on bargain purchase — — 22,049 — Other income (expense), net (313 ) (1,537 ) (807 ) (536 ) Loss before income tax expense (48,573 ) (28,256 ) (112,535 ) (162,959 ) Income tax credit/(expense) 656 (994 ) (1,336 ) (2,497 ) Net loss attributable to ordinary shareholders $ (47,917 ) $ (29,250 ) $ (113,871 ) $ (165,456 ) Net loss per ordinary share Basic and diluted $ (0.04 ) $ (0.03 ) $ (0.09 ) $ (0.17 ) Weighted average shares outstanding: Basic and diluted 1,362,672,380 984,715,238 1,206,440,978 967,242,403 Condensed Consolidated Balance Sheets (unaudited, in thousands, except share data) December 31, December 31, 2023 2022 Assets Current assets Cash and cash equivalents $ 143,991 $ 108,033 Marketable securities - available-for-sale debt securities (amortized cost of $2,940 and $97,501) net of allowance for expected credit losses of $0 and $0 2,947 96,572 Accounts receivable, net of allowance for expected credit losses of $0 and $0 821 7,435 Other current assets and prepaid expenses 59,793 43,330 Total current assets 207,552 255,370 Restricted cash 3,026 1,569 Operating lease right-of-use assets, net of accumulated amortization of $13,220 and $9,470 20,762 18,019 Property, plant and equipment, net of accumulated depreciation of $46,020 and $38,588 50,946 53,516 Intangible assets, net of accumulated amortization of $5,155 and $4,676 330 442 Total assets $ 282,616 $ 328,916 Liabilities and stockholders' equity Current liabilities Accounts payable $ 8,128 $ 4,753 Operating lease liabilities, current 5,384 2,728 Accrued expenses and other current liabilities 30,303 31,215 Restructuring provision — 2,285 Deferred revenue, current 28,973 23,520 Total current liabilities 72,788 64,501 Operating lease liabilities, non-current 19,851 20,349 Deferred revenue, non-current 149,060 160,892 Other liabilities, non-current 1,404 1,296 Total liabilities 243,103 247,038 Stockholders' equity Common stock - Ordinary shares par value £0.001, 1,702,760,280 authorized and 1,363,008,102 issued and outstanding (2022: 1,282,773,750 authorized and 987,109,890 issued and outstanding) 1,865 1,399 Additional paid in capital 1,064,569 990,656 Accumulated other comprehensive loss (3,748 ) (875 ) Accumulated deficit (1,023,173 ) (909,302 ) Total stockholders' equity 39,513 81,878 Total liabilities and stockholders' equity $ 282,616 $ 328,916 Condensed Consolidated Cash Flow Statement (unaudited, in thousands) Year ended Year ended December 31, December 31, 2023 2022 Cash flows from operating activities Net loss $ (113,871) $ (165,456) Adjustments to reconcile net loss to net cash used in operating activities: Depreciation 9,453 5,266 Amortization 387 809 Gain on bargain purchase (22,049 ) — Share-based compensation expense 11,773 18,240 Unrealized foreign exchange losses/(gains) 198 (2,438 ) (Accretion)/amortization on available-for-sale debt securities (1,986 ) 2,525 Other 167 816 Changes in operating assets and liabilities: Increase in receivables and other operating assets (1,291 ) (9,813 ) (Decrease)/increase in payables and other current liabilities (9,087 ) 4,408 (Increase)/decrease in deferred revenue (14,574 ) 3,874 Net cash used in operating activities (140,880 ) (141,769 ) Cash flows from investing activities Acquisition of property, plant and equipment (4,681 ) (29,496 ) Acquisition of intangible assets (199 ) (244 ) Cash from acquisition of TCR2 Therapeutics Inc. 45,264 — Maturity or redemption of marketable securities 210,983 166,994 Investment in marketable securities (75,953 ) (48,117 ) Other 1,124 — Net cash provided by investing activities 176,538 89,137 Cash flows from financing activities Proceeds from issuance of common stock from offerings, net of commissions and issuance costs 624 12,817 Proceeds from exercise of stock options 256 50 Net cash provided by financing activities 880 12,867 Effect of currency exchange rate changes on cash, cash equivalents and restricted cash 877 (2,299 ) Net increase/(decrease) in cash, cash equivalents and restricted cash 37,415 (42,064 ) Cash, cash equivalents and restricted cash at start of period 109,602 151,666 Cash, cash equivalents and restricted cash at end of period $ 147,017 $ 109,602 Supplemental cash flow information Interest received $ 4,748 $ 5,149 Accretion/(amortization) on available-for-sale debt securities 1,986 (2,525 ) Income taxes paid (4,000 ) (630 ) Adaptimmune Contacts Investor Relations Juli P. Miller, Ph.D. — VP, Corporate Affairs and Investor Relations T: +1 215 825 9310 M: +1 215 460 8920 Juli.Miller@adaptimmune.com Media Relations Dana Lynch, Senior Director of Corporate Communications M: +1 267 990 1217 Dana.Lynch@adaptimmune.com a - "Synovial Sarcoma." National Cancer Institute. Accessed 11 December 2023. b - 1: Aytekin MN, et al. J Orthop Surg (Hong Kong). 2020;28(2) 2: Disease-specific survival from Hoffman et al. (2013), Localized and metastatic 3: 67% of synovial sarcoma tumors express MAGE-A4. MAGE-A4 expression based on ADAP samples and expression cut off criteria of ≥30% tumor cells at ≥2+ intensity. Synovial sarcoma and MRCLS MAGE-A4 expression based on 1,043 patient samples at November 20, 2020 data cut-off and expression of all other tumor types on 6,167 patients, 1,543 tumor samples at November 19, 2021 data cut-off 4: 70-90% of SyS and MRCLS tumors express NY-ESO-1Endo M, de Graaff MA, Ingram DR, et al. NY-ESO-1 (CTAG1B) expression in mesenchymal tumors. Mod Pathol 2015; 28: 587-95. Jungbluth AA, Chen YT, Stockert E, Busam KJ, Kolb D, Iversen K, et al. Immunohistochemical analysis of NY-ESO-1 antigen expressionin normal and malignant human tissues. Int J Cancer 2001;92:856-60. 5: HLA A2 expression based on ADAP samples of 41% for synovial sarcoma and MRCLS (1,043 patient samples; data cut-off November 20, 2020) 1 Total liquidity is a non-GAAP financial measure, which is explained and reconciled to the most directly comparable financial measures prepared in accordance with GAAP below To view the source version of this press release, please visit

Gastric cancer, ovarian cancer, myxoid/round cell liposarcoma and synovial sarcoma selected as initial clinical indications for lead program MDG1015 MDG1015 is a first-in-class, third generation TCR-T therapy targeting NY-ESO-1/ LAGE-1a, armored and enhanced by costimulatory switch protein PD1-41BB Clinical development in both orphan and more common cancer indications addresses high unmet medical need in large patient populations February 12, 2024. Medigene AG (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, today announced the selection of gastric cancer, ovarian cancer and two types of soft tissue sarcomas, myxoid/round cell liposarcoma and synovial sarcoma, as the initial clinical indications for its lead candidate MDG1015. MDG1015 is a first-in-class, third generation T cell receptor engineered T cell (TCR-T) therapy targeting NY-ESO-1/LAGE-1a (New York esophageal squamous cell carcinoma 1 / L Antigen Family Member-1a), armored and enhanced by costimulatory switch protein PD1-41BB in the context of HLA-A*02 (HLA, human leukocyte antigen). Preclinical data presented in 2023 at the AACR and ESMO conferences demonstrated the clear potential of MDG1015 to improve clinical outcomes in solid tumors. “The selection of these cancers as targets for MDG1015 is an important step as we advance towards the first-in-human trial. Following recent positive EU and US preliminary regulatory interactions, we remain on track for an IND/CTA approval in the second half of 2024,” said Dr. Selwyn Ho, Chief Executive Officer at Medigene. “While clinical data for engineered cell therapies still in development has shown benefits in some of the selected indications, we believe there is still significant room for improvement in terms of efficacy and durability of progression-free survival. We are confident that MDG1015 as a first-in-class armored and enhanced TCR-T therapy has the potential to address these challenges and improve the quality of life of patients suffering with cancer." The indications were selected predominantly based on target and/or PD-L1 expression, with 34-60%, 35-55% and 75-80% of gastric cancer, ovarian cancer and the two subtypes of soft tissue sarcoma expressing NY-ESO-1/LAGE-1a, respectively.i,ii,iii Additional MDG1015 preclinical data will be presented at upcoming scientific conferences in 2024. Within the current treatment landscape, high NY‑ESO-1 expression is associated with a worse prognosisiv and expression increases with advanced disease stage.iv,v When looking only at the initially selected solid cancer indications, it is estimated that over 100,000 patients in the world’s top eight economies could be eligible for treatment with MDG1015 based on yearly incidence, target expression and HLA-A*02 positivity. These cancers are also marked by a clear need for new treatment modalities, with estimated five-year survivals for advanced gastric cancer, ovarian cancer and the two subtypes of soft tissue sarcoma as low as 5%-31%.vi Gastric cancer represents the fifth most common cause of cancer deaths worldwidevii and 90% of all gastric cancers are gastric adenocarcinomas (GACs).viii Overall, ∼60% of people with GAC are not eligible for curative treatment owing to late presentation or comorbidities.viii The 36% of US patients diagnosed with distant metastases have a mere 6.6% 5‑year relative survival rate.vi Ovarian cancer is one of the leading causes of cancer deaths among women, and in 55% of US patients distant metastases are present at the time of diagnosis.vi Despite advances in treatment, the prognosis remains poor with a 5-year relative survival rate of 31% for US epithelial ovarian cancer patients with advanced disease.vi Myxoid/round cell liposarcoma is a type of soft tissue sarcoma originating from the fat cells and typically affects younger patients between 30–50 years of age. This disease has an incidence of up to ~1,350 patients in the US which makes it an orphan indication.vi For patients with advanced disease there is an 8% 5-year disease-specific survival rate.ix Synovial sarcoma is a type of soft tissue sarcoma characterized by its development in cells around joints and tendons and most often affects adolescents and young adults. The disease has an incidence in line with myxoid liposarcoma, of up to ~1,300 patients in the US making it an orphan indication.vi In 50% of synovial sarcoma cases the disease metastasizes to other areas of the body, most commonly to the lungs. For patients with advanced stage disease, the median overall survival at or after second line therapy is under a year and the 5-year overall survival is 10%.vi,x Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing differentiated T cell therapies for treatment of solid tumors. Its End-to-End Platform is built on multiple proprietary and exclusive technologies that enable the Company to generate optimal T cell receptors against both cancer testis antigens and neoantigens, armor and enhance these T cell receptor engineered (TCR) -T cells to create best-in-class, differentiated TCR-T therapies, and optimize the drug product composition for safety, efficacy and durability. The End-to-End Platform provides product candidates for both its own therapeutics pipeline and partnering. Medigene’s lead TCR-T program MDG1015 is expected to receive IND/CTA approval in the second half of 2024. For more information please visit https://medigene.com/ MDG1015 is a first-in-class, 3rd generation T cell receptor engineered T cell (TCR-T) therapy targeting NY-ESO-1/ LAGE-1a, a well-recognized and validated cancer testis antigen, which is expressed in multiple tumor types. MDG1015 contains our optimal affinity 3S (sensitive, specific and safe) NY-ESO-1/LAGE-1a TCR combined with our proprietary PD1-41BB costimulatory switch protein that blocks the PD1/PD-L1 inhibitory axis while simultaneously activating the T cell through the well described -41BB pathway further enhancing the activity and persistence of the TCR-T in the hostile tumor microenvironment. MDG1015 is currently undergoing IND/CTA enabling studies with IND/CTA approval expected in the second half of 2024. Checkpoint inhibition via PD-1/PD-L1 pathway: Cells of solid tumors are sensitive to killing by activated T cells but can escape this killing activity by producing inhibitory molecules known as ‘checkpoint proteins’, such as the Programmed Death Ligand 1 (PD-L1), on their surface. When this occurs, activated T cells which express PD-1, the natural receptor for PD-L1, are inactivated. The expression of PD-L1 is an adaptive immune resistance mechanism for tumors that can help them survive and grow. The 4-1BB (CD137) costimulatory signaling pathway: Effective T cell immune responses to antigens typically require both a primary antigenic stimulation via the T cell receptor (TCR) and costimulatory signals. The intracellular signaling domains of the 4-1BB protein offer a well-characterized pathway of costimulation and enhanced T cell responses. Medigene’s PD1-41BB switch receptor turns the tumor’s attempted self-defense mechanism against the tumor by substituting the inhibitory signaling domain of PD-1 with the activating signaling domain of 4‑1BB. Therefore, instead of inactivating T cells, the switch receptor delivers an activating signal to TCR-T cells. PD1-41BB-modified TCR-T cells proliferate strongly in the presence of PD-L1-positive tumor cells and kill more tumor cells upon repeated exposure. Additionally, switch receptor signals enable TCR-T cells to function better with low levels of glucose or high levels of TGFß, two conditions characteristic of strongly hostile tumor microenvironments. This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only. i Blouch et al, Annals of Oncology (2021) 32 (suppl_5): S382-S406. 10.1016/annonc/annonc686 ii Odunsi K, et al. Cancer Res. 2003 Sep 15 ;63(18) :6076-83 iii Lai JP, Robbins PF, Raffeld M, et al. NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis. Mod Pathol. 2012;25(6):854-858. doi:10.1038/modpathol.2012.31 iv Raza A, et al. J Transl Med 2020 Mar 27;18(1):140. https://doi.org/10.1186/s12967-020-02306-y v Aung PP, et al. Hum. Pathol. 2014 Feb; 45(2): 259–267. https://doi.org/10.1016/j.humpath.2013.05.029 vi The American Cancer Society, Cancer Statistics Center, SEER database htps://cancerstatisticscenter.cancer.org [accessed 05Feb2024] vii Global Cancer Observatory https://gco.iarc.fr/today [accessed 05Feb2024] viii Lordick et al. An. of Oncol. volume 33, issue 10, p1005-1020, October 2022 Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. https://doi.org/10.1016/j.annonc.2022.07.004 ix Disease-specific survival from Hoffman et al. (2013), Localized and metastatic myxoid/round cell liposarcoma. Cancer, 119: 1868-1877 x Carroll C, Patel N, Gunsoy NB, Stirnadel-Farrant HA, Pokras S. Meta-analysis of pazopanib and trabectedin effectiveness in previously treated metastatic synovial sarcoma (second-line setting and beyond). Future Oncol. 2022;18(32):3651-3665. doi:10.2217/fon-2022-0348 The content above comes from the network. if any infringement, please contact us to modify.

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Incendia Therapeutics, formerly Parthenon Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), today announced that it will have two poster presentations at the European Society for Medical Oncology (ESMO) Congress 2023, to be held in Madrid, Spain October 20-24, 2023. The company will present data on the expression of discoidin domain receptor 1 (DDR1) mRNA and protein across 20 tumor types and will provide a detailed overview of Incendia’s Phase 1 first-in-human clinical trial for its lead candidate PRTH-101 in patients with advanced solid tumors (NCT05753722). “The tumor microenvironment is dramatically impacted by the over expression of DDR1 and its role in the alignment of collagen fibers, which ultimately prevents immune cells from being able to directly interact with tumors,” said Laura Dillon, Vice President of Translational Medicine and Bioinformatics at Incendia. “These data presented at ESMO further highlight the potential of PRTH-101 as a first-in-class DDR1 inhibitor that may address the unmet need in the numerous cancers with high DDR1 expression.” Presentation Details: Title: High DDR1 mRNA and Protein Expression Across Human Tumor Types Correlate with Epithelial Composition of the Tumor Microenvironment Lead author: Laura Dillon, Ph.D., Vice President, Translational Medicine and Bioinformatics at Incendia Therapeutics Presentation #: 2309P Presentation Time: Saturday, October 21, 12:00 - 1:00 PM CEST (6-7 AM ET) Translational Research (agnostic) Key Highlights: DDR1 is expressed in a high proportion of tumor cells across a range of epithelial tumor types, suggesting potentially broad application of DDR1-targeted therapies. A high proportion of tumor cells (median of 0.76) expressed DDR1 across all epithelial tumor types. DDR1 expression was uniformly low in mesenchymal tumors (median of 9 cells/mm2) compared to epithelial tumors (median of 2803 cells/mm2). Moderate correlation was observed between DDR1 mRNA expression and DDR1+ cell density across tumor types (R=0.48, p<0.0001). In epithelial tumors, both DDR1 mRNA and protein expression were correlated with the percentage of epithelium (R=0.37 and 0.56, respectively; both p<0.0001), with significant variance between tumor types. Title: A Phase 1 First-in-Human Study of PRTH-101, an IgG1 Monoclonal Antibody Targeting DDR1, as a Monotherapy and Combined with Pembrolizumab in Patients with Advanced Solid Malignancies Lead author: Shiraj Sen, M.D., Ph.D., Medical Oncologist and Director of NEXT Oncology Dallas Presentation #: 1079TiP Presentation Time: Monday, October 23, 12:00 – 1:00 PM CEST (6-7 AM ET) (Investigational immunotherapy) Key Highlights: Discoidin domain receptor 1 (DDR1) is a collagen receptor that represents a promising therapeutic target due to its role in excluding lymphocytes from the tumor microenvironment (TME) by aligning collagen fibers. DDR1 expression is high in multiple cancer types and associated with worse survival. PRTH-101 is a humanized IgG1 antibody that binds to the extracellular domain of both membrane-bound and soluble DDR1. In preclinical models, PRTH-101 monotherapy resulted in disruption of aligned collagen fibers in the tumor stroma, increased infiltration of lymphocytes, and tumor growth inhibition. When PRTH-101 is combined with PD-1 inhibition, activated T cell infiltration is increased compared to PRTH-101 alone. This is a Phase 1 first-in-human study that will evaluate intravenous PRTH-101 +/- pembrolizumab in patients with advanced solid tumors. Safety, efficacy, pharmacokinetic, and pharmacodynamic endpoints will be monitored and reported. The first part of the study (Ph1a) seeks to identify the maximum tolerated dose (MTD) or optimal biologic dose (OBD), of PRTH-101 to determine the recommended phase 2 dose (RP2D). The second part (Ph1b) seeks to identify the MTD or OBD of PRTH-101 in combination with pembrolizumab to determine the PRTH-101 combination RP2D. The third part (Ph1c) consists of dose expansion in disease-directed cohorts to assess the anti-tumor efficacy of PRTH-101 monotherapy and/or combination therapy. About PRTH-101 PRTH-101 is a therapeutic antibody that specifically binds to and blocks discoidin domain receptor 1 (DDR1,) a protein expressed on tumor cells that binds collagen to make a physical barrier that prevents immune cells from interacting with and attacking tumor cells. By disabling DDR1, the collagen fibers lose alignment and loosen, creating gaps in the tumor barrier, thus allowing T-cells to enter and attack the tumor. Blockade of DDR1 represents a unique approach to stimulating immune-based antitumor activity, and in preclinical models such blockade shows both single agent anti-tumor activity as well as marked augmentation of immunity enhanced by PD-1 blockade. Tumor types that express high levels of DDR1-associated collagen barriers include colorectal, ovarian, and non-small cell lung cancer. Currently, there are no approved drugs that target DDR1. About Incendia Therapeutics Incendia Therapeutics is discovering and developing a novel class of anti-cancer therapies that reprogram the tumor microenvironment (TME). Recent research has shown that the interplay between tumor cells and their surrounding TME results in the creation of barriers that markedly attenuate the immune system’s ability to attack the tumor. Based on rigorous, groundbreaking research, Incendia is developing a portfolio of drug candidates to treat select patients at the appropriate/ideal stage in disease progression. For more information visit incendia.com and LinkedIn.