KRAS G12D

September 25, 2024 – Medigene AG (Medigene or the “Company”, FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, today announced the filing of a new patent application protecting MDG2021, a T cell receptor engineered T cell (TCR-T) therapy targeting Kirsten rat sarcoma viral oncogene homologue (KRAS) G12D with human leukocyte antigen (HLA)-A*11, for the TCR-T therapy alone as well as in combination with the Company’s PD1-41BB costimulatory switch protein (CSP) technology to the European Patent Office. MDG2021 marks the second candidate within the KRAS library targeting KRAS G12D (HLA-A*11) for which the Company announced lead selection in June 2024. The addition of MDG2021 to Company’s KRAS targeting TCR library significantly impacts the addressable patient population with the combination of KRAS G12V and KRAS G12D mutations comprising ~50% of all KRAS mutations in all tumors (pan-cancer), or even >70% in pancreatic adenocarcinoma. (Yang et al., J Clin Med 2023) “We are pleased to announce the patent filing for MDG2021, our optimal affinity 3S (sensitive, specific and safe) TCR targeting KRAS G12D (HLA-A*11), alone and in combination with our PD1-41BB armoring and enhancement CSP,” said Selwyn Ho CEO at Medigene. “This filing reaffirms our commitment to broaden our intellectual property for TCRs targeting both neoantigens and cancer testis antigens that have potential utility in multiple TCR-guided treatment modalities including TCR-T therapies such as MDG2021, as well as TCR-guided T cell engager therapies (MDG3010) and TCR-natural killer cell therapies.” Medigene continually extends and strengthens its patent portfolio with new technologies and expands existing patents into additional jurisdictions. The Company maintains 29 different patent families worldwide covering applications protecting Medigene’s 3S TCRs as well as its exclusive E2E Platform technologies. Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing T cell receptor (TCR)-guided therapies to effectively eliminate cancer. Its End-to-End Platform generates optimal 3S (sensitive, specific and safe) T cell receptors with unique and distinctive attributes that are utilized in multiple therapeutic modalities, such as T cell receptor engineered T cell (TCR-T) therapies, TCR-guided T cell engager therapies and TCR-natural killer cell therapies for both its in-house product pipeline and partnering. Medigene’s lead TCR-T program MDG1015 is a potential best-in-class, TCR-T therapy to treat multiple solid tumor indications. The End-to-End Platform technologies enable armoring and enhancing of these T cells to overcome the immunosuppressive tumor microenvironment (TME) and ensure the T cell drug product composition maximizes safety, efficacy and durability of response. Medigene’s MDG1015 received IND approval in Q3 2024 and is filing for CTA in Q4 2024. For more information, please visit https://medigene.com/ Medigene’s approach to immunotherapy harnesses the immense power of natural T cell receptors. By combining these TCRs with different components of the immune system such as T cells, natural killer (NK) cells or a CD3 complex (TCE, T cell engager), highly specific, sensitive and safe modalities are formed to either complement and/or activate the body’s defense systems against cancer. Medigene’s comprehensive End-to-End (E2E) Platform is built on a foundation of proprietary and cutting-edge technologies, driving the development of highly specific TCR-guided therapies, including the latest advancements in TCR-T, TCR-NK and TCR-TCE drug products. The E2E Platform incorporates sophisticated TCR generation and optimization techniques, such as Allogeneic-HLA TCR Priming, and integrates advanced product armoring and enhancement features like PD1-41BB and CD40L-CD28 Costimulatory Switch Proteins, and iM-TCR. In addition, the E2E Platform offers solutions to developing optimal cell therapy drug products for improved safety, efficacy and durability. Collaborations with partners like BioNTech, Regeneron and WuXi Biologics further underscore the platform’s capabilities and its potential to revolutionize cancer treatment. 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. The content above comes from the network. if any infringement, please contact us to modify.

Planegg/Martinsried, September 14, 2024. Medigene AG (Medigene or the “Company”, FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, presented updates for its T cell receptor (TCR) library targeting the Kirsten rat sarcoma viral oncogene homolog (KRAS) and also highlighted advancements of its UniTope and TraCR technology, which serves as a universal system for tagging and tracking recombinant TCRs (rTCRs) across multiple modalities, including T cell receptor engineered T cell (TCR-T) therapies, at the ESMO Congress 2024 taking place in Barcelona from September 13-17, 2024. The presented posters “Advancing a multi-dimension KRAS mutation-specific T cell receptor (TCR) library with a 3S TCR targeting the G12D mutation to address large global patient populations” and “UniTope & TraCR - Universal tagging and tracking system for TCR-T cells integrated directly in the TCR constant region” will be made available after the conference on Medigene’s website: https://medigene.com/science/abstracts/ "We are excited about our expanding library of mKRAS-specific rTCRs targeting different mutations and HLA allotypes, aiming to broaden treatment options and improve outcomes for patients with difficult-to-treat solid tumors," said Dolores Schendel, CSO at Medigene AG. "Our lead KRAS G12D candidate, enhanced by the costimulatory switch protein (CSP) PD1-41BB, has shown very promising T cell functionality. By overcoming the challenges of the tumor microenvironment that have hindered the effectiveness of TCR-T therapies, we are confident that this program could offer best-in-class efficacy and safety. We are expanding our TCR library and also incorporating new proprietary technologies into our End-to-End (E2E) Platform, including UniTope & TraCR, a universal detection system for any rTCR across various modalities like TCR-T therapies, TCR-guided T cell engagers therapies, and TCR-NK cell therapies. Direct integration of the UniTope tag guarantees 100% co-expression of a unique identifier in a rTCR sequence and provides a significant advancement over current methods for detection of rTCRs in TCR-guided therapeutics. UniTope and TraCR will help us streamline quality control and provide precise data for determining the correct drug dosing for TCR-T therapies." Advancing a multi-dimension KRAS mutation-specific T cell receptor (TCR) library with a 3S TCR targeting the G12D mutation to address large global patient populations The first data presented showcased recent advancements in the expansion of the Company's KRAS library, using a high-throughput approach to develop optimal affinity TCRs targeting the mKRAS G12D neoantigen in the context of HLA-A*11 via Medigene’s proprietary E2E Platform. Further in vitro studies characterized the lead TCR candidate in terms of specificity, sensitivity, and safety (3S) while incorporating the PD1-41BB CSP. TCR-expressing T cells, when stimulated by mKRAS G12D-positive tumor cells, showed increased interferon gamma (IFNγ) release. Reduced cancer cell survival was observed when mKRAS G12D-positive tumor cell lines from various origins were exposed to T cells co-expressing the rTCR mKRAS G12D-HLA-A*11 and PD1-41BB CSP. These effects were specific to mKRAS G12D, with no impact on wild-type KRAS cells. The TCR demonstrated an excellent safety profile, with no off-target toxicity against an extensive panel of healthy cell types. Finally, in vitro data showed that co-expression of PD1-41BB CSP enhanced and sustained T cell function in an rTCR-specific manner, with gated activation that only occurred when the specific peptide-HLA complex was present on target cells, and not through PD-L1 expression alone. UniTope & TraCR - Universal tagging and tracking system for TCR-T cells integrated directly in the TCR constant region The second poster displayed the Company´s recently introduced universal TCR tagging and tracking combination technology UniTope & TraCR. Bioinformatic alignment of T cell receptor beta variable sequences enabled a six-amino-acid peptide (UniTope) to be predicted that is not found in natural TCR beta chains and has low immunogenicity. In parallel, an antibody was developed to specifically target this short amino acid peptide (TraCR) and further in vitro experiments demonstrated that TCR-T cells containing the UniTope sequence exhibited similar effects to those of TCR-T cells without the UniTope sequence. Integration of the UniTope sequence in a rTCR guarantees 100% co-expression of the tag and provides a significant advancement over current methods of detection of rTCRs in TCR-guided therapeutics. In vitro studies confirmed that insertion of UniTope did not alter expression or functionality of rTCRs. In addition, safety assessments confirmed that UniTope-modified rTCRs displayed the same high safety profile as un-modified rTCRs with respect to lack of recognition and killing of 16 healthy cell types. --- end of press release --- About Medigene AG Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing T cell receptor (TCR)-guided therapies to effectively eliminate cancer. Its End-to-End Platform generates optimal 3S (sensitive, specific and safe) T cell receptors with unique and distinctive attributes that are utilized in multiple therapeutic modalities, such as T cell receptor engineered T cell (TCR-T) therapies, TCR-guided T cell engager therapies and TCR-natural killer cell therapies for both its in-house product pipeline and partnering. Medigene’s lead TCR-T program MDG1015 is a potential best-in-class, TCR-T therapy to treat multiple solid tumor indications. The End-to-End Platform technologies enable armoring and enhancing of these T cells to overcome the immunosuppressive tumor microenvironment (TME) and ensure the T cell drug product composition maximizes safety, efficacy and durability of response. Medigene’s MDG1015 received IND approval in Q3 2024 and is filing for CTA in Q4 2024. For more information, please visit https://medigene.com/ About Medigene’s End-to-End Platform Medigene’s approach to immunotherapy harnesses the immense power of natural T cell receptors. By combining these TCRs with different components of the immune system such as T cells, natural killer (NK) cells or a CD3 complex (TCE, T cell engager), highly specific, sensitive and safe modalities are formed to either complement and/or activate the body’s defense systems against cancer. Medigene’s comprehensive End-to-End (E2E) Platform is built on a foundation of proprietary and cutting-edge technologies, driving the development of highly specific TCR-guided therapies, including the latest advancements in TCR-T, TCR-NK and TCR-TCE drug products. The E2E Platform incorporates sophisticated TCR generation and optimization techniques, such as Allogeneic-HLA TCR Priming, and integrates advanced product armoring and enhancement features like PD1-41BB and CD40L-CD28 Costimulatory Switch Proteins, and iM-TCR. In addition, the E2E Platform offers solutions to developing optimal cell therapy drug products for improved safety, efficacy and durability. Collaborations with partners like BioNTech, Regeneron and WuXi Biologics further underscore the platform’s capabilities and its potential to revolutionize cancer treatment. About KRASKRAS (Kirsten rat sarcoma viral oncogene homologue) belongs to the group of small so-called Guanosine-5′-triphosphate (GTP)-binding proteins, known as RAS-like GTPases. Under physiological conditions KRAS tightly regulates cell proliferation and survival. In cancer, KRAS is found frequently altered, in a wide variety of often fatal solid cancer types like pancreatic ductal adenocarcinoma, non-small-cell lung cancer, and colorectal cancer. Mutations in the KRAS gene result in the creation of neoantigens which drive uncontrolled proliferation of cancer cells. These mutations within the KRAS gene are unique to cancer cells and absent in healthy normal tissue, making KRAS an attractive target for TCR-T therapies. T cell receptor engineered T cell therapies offer a promising approach to targeting these mutations and addressing the challenges posed by solid tumors. Unlike CAR-T cells, which require surface antigens for recognition and may have limitations in target accessibility, TCR-T cells recognize a broader range of targets including intracellular proteins like neoantigens. This unique ability makes TCR-T therapies particularly well-suited for targeting KRAS mutations and other challenging neoantigens. About Medigene’s PD1-41BB Costimulatory Switch Protein 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 to 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. Medigene AG Pamela Keck Phone: +49 89 2000 3333 01 E-mail: investor@medigene.com In case you no longer wish to receive any information about Medigene, please inform us by e-mail (investor@medigene.com). We will then delete your address from our distribution list.

LONDON--( BUSINESS WIRE )-- Silexion Therapeutics (NASDAQ: SLXN) has emerged an intriguing yet under the radar player in the precision oncology space, focusing on developing innovative RNA interference (RNAi) therapies for KRAS-driven cancers. As a recently de-SPACed company following its merger with Moringa Acquisition Corp (NASDAQ: MACA), Silexion presents an interesting opportunity in the rapidly growing field of targeted cancer treatments, particularly in addressing the challenges of pancreatic and potentially other KRAS-driven cancers. Technology Deep Dive: LODER™ and SIL-204 At the core of Silexion's approach is its proprietary LODER™ (Local Drug EluteR) platform, which has demonstrated encouraging results in Phase 2 clinical trials for locally advanced pancreatic cancer. The company's technology stands out due to two key pharmacological functions: oncogene silencing and localized delivery. Silexion's siRNA actively prevents cells from producing oncogenic proteins, contrasting with small molecule KRAS inhibitors that target already-oncogenic proteins. Additionally, the LODER™ system bypasses the tumor barrier, allowing for higher concentrations of treatment directly within the tumor, enhancing efficacy while reducing systemic side effects. Silexion's second-generation improved product, SIL-204, is an optimized siRNA formulation expected to enter Phase 2/3 clinical trials in 2025-2026. SIL-204 represents a significant advancement in RNAi technology, with the potential to target a broader range of KRAS mutations (pan KRAS G12x). This is particularly important as it addresses a wider spectrum of KRAS-driven cancers compared to current small molecule KRAS inhibitors, which are limited to targeting KRAS G12C (found in only 1-2% of pancreatic cancer cases). The Context: The Challenges in Treating Pancreatic Cancer Pancreatic cancer remains one of the most challenging malignancies to treat, with a dismal five-year survival rate of just 12.8%. Several factors contribute to the difficulty in treating this aggressive cancer. Late detection is a major issue, as pancreatic cancer is often diagnosed at advanced stages due to a lack of early symptoms and effective screening methods. The aggressive nature of pancreatic tumors, characterized by rapid growth and early metastasis, further complicates treatment efforts. The dense tumor microenvironment of pancreatic cancer creates a significant barrier to drug penetration, reducing the effectiveness of traditional chemotherapies. Additionally, the genetic complexity of pancreatic cancer, with KRAS mutations present in over 90% of cases, has proven difficult to target effectively with conventional therapies. Compounding these challenges is the tendency of pancreatic cancer cells to develop resistance to standard chemotherapies, leading to poor long-term outcomes. Silexion's LODER™ and SIL-204 technologies are designed to address these challenges directly. By silencing KRAS mutations at the genetic level and delivering treatment locally, Silexion's approach has the potential to overcome the barriers that have historically limited the effectiveness of pancreatic cancer treatments. Clinical Progress and Future Potential Silexion's LODER™ technology has already shown promising results in Phase 2 clinical trials for locally advanced pancreatic cancer. Key findings include a 9.3-month improvement in overall survival when LODER™ was combined with standard chemotherapy, compared to chemotherapy alone in patients with non-resectable pancreatic cancer harboring KRAS G12D/V mutations. The study also revealed an increased objective response rate (ORR) of 55% with LODER™ plus chemotherapy, compared to 20% for standard chemotherapy alone. Notably, the ORR increased to 64% when considering tumors that were initially non-resectable becoming resectable. These results are particularly encouraging given the historically poor outcomes in pancreatic cancer treatment. As SIL-204 moves into Phase 2/3 trials, there is potential for even greater efficacy due to its optimized formulation and broader targeting of KRAS mutation. Expanding Beyond Pancreatic Cancer: Treating Other KRAS-Driven Cancers While Silexion's initial focus has been on pancreatic cancer, the company's innovative RNAi technology and LODER™ platform have significant potential for application in other KRAS-driven cancers. This broader applicability could substantially expand Silexion's market opportunity and impact in the field of precision oncology. The company's pipeline includes plans to target additional types of pancreatic cancer as well as other cancers driven by KRAS mutations. One notable area of potential expansion is colorectal cancer, which is often associated with KRAS mutations and represents a significant unmet medical need. The ability of Silexion's technology to target a broader range of KRAS mutations (pan KRAS G12x) compared to current small molecule inhibitors positions the company favorably for addressing multiple cancer types. This versatility could prove particularly valuable as KRAS mutations are found in various cancers beyond pancreatic, including lung and colorectal cancers. Moreover, the localized delivery system of the LODER™ platform could potentially be adapted for use in other solid tumors, offering a unique advantage in treating cancers that are challenging to target with systemic therapies. This adaptability could open up new avenues for Silexion in treating a wider array of difficult-to-treat cancers. As Silexion advances its clinical trials and potentially expands into these additional indications, it could significantly broaden its addressable market. This expansion potential not only enhances the company's value proposition but also aligns with the growing trend in precision medicine towards developing versatile platforms that can address multiple cancer types driven by similar genetic mutations. Market Potential: Big Pharma's Growing Appetite for Precision Oncology The precision medicine market, particularly in oncology, is experiencing explosive growth, with major pharmaceutical companies like Pfizer aggressively seeking innovative assets to bolster their pipelines. This trend is driven by the projected expansion of the global precision medicine market from $102.17 billion in 2024 to a staggering $470.53 billion by 2034, growing at a CAGR of 16.5%. Within this broader market, KRAS-driven cancers represent a substantial unmet need, with the market for KRAS inhibitors expected to grow at an impressive 36% CAGR, reaching $10 billion by 2032. This rapid growth has sparked a flurry of M&A activity in the precision oncology space, as exemplified by several high-profile acquisitions. For example , Pfizer's landmark $43 billion acquisition of Seagen in 2023, which doubled Pfizer's oncology pipeline and highlighted the growing importance of antibody-drug conjugates (ADCs) and precision oncology treatments. Similarly, AbbVie's $10.1 billion purchase of Immunogen, following the FDA approval of Elahere, a targeted therapy for ovarian cancer, demonstrating the high value placed on innovative, precision-targeted treatments. These deals underscore the willingness of big pharma to invest heavily in cutting-edge oncology assets, particularly those addressing difficult-to-treat cancers with novel approaches. Silexion's focus on RNAi technology for KRAS-driven cancers, especially its innovative approach to pancreatic cancer treatment, positions it as a potentially attractive acquisition target in this landscape. The company's technologies, which have shown initial promising results in clinical trials, seem to align well with the industry trend towards more targeted and personalized cancer therapies. As large pharmaceutical companies continue to seek differentiated assets to fill gaps in their oncology portfolios, Silexion's unique technology and focus on high-unmet-need cancers could make it a valuable addition to a larger company's pipeline. Moreover, with major pharmaceutical companies collectively holding over $170 billion in cash reserves, according to recent reports , the M&A environment seems highly favourable for innovative companies like Silexion. This trend, combined with Silexion's potential to address the challenges of pancreatic cancer - a disease with a dismal five-year survival rate of just 12.8% - positions the company at the intersection of high market demand and critical unmet medical need. Looking Ahead Silexion Therapeutics represents a unique approach in the fight against KRAS-driven cancers, particularly pancreatic cancer. Its innovative RNAi technology, delivered via the LODER™ platform and the promising SIL-204, seems to address many of the challenges that have historically limited progress in treating these aggressive cancers. As the company advances its clinical trials and potentially potential eyes other KRAS-driven cancers, it stands at the forefront of a new era in precision oncology. While the road ahead in drug development is always challenging, Silexion's progress to date and the potential of its technology make it a company to watch in the evolving landscape of cancer treatment. As with any early-stage biotech company, potential stakeholders should conduct thorough due diligence, considering both the promising technology and market opportunity alongside the inherent risks in drug development. PESG Research is a digital research and coverage brand, offering commentary and exploration into the current and future state of the Pharma, BioTech and Sustainability and other industries. * * * This report is for informational purposes only and is not intended to serve as medical financial, investment or any form of professional advice, recommendation or endorsement. Please review the full documentation detailing financial compensation disclosures and disclaimers the text is subject to. PESG Research is a digital brand that has been compensated to publish and syndicate commentary and exploration into innovative companies and industries and it is subject to conflicts of interest as detailed in the full documentation. 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