ERK x ERK1 x ERK2

Five posters showcased progress with multiple preclinical and clinical programs, including ATG-008 (mTORC1/2 inhibitor), ATG-017 (ERK1/2 inhibitor), ATG-037 (CD73 inhibitor), ATG-031 (anti-CD24 monoclonal antibody) and ATG-034 (LILRB4 antagonist antibody) Clinical results showed promising efficacy of ATG-008 in patients with advanced HBV+ HCC, especially those who had received CPIs SHANGHAI and HONG KONG, April 17, 2023 /PRNewswire/ -- Antengene Corporation Limited ( "Antengene" SEHK: 6996.HK), a leading innovative, global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for cancer, today announced the presentation of five posters at the American Association for Cancer Research Annual Meeting 2023 Meetings ( AACR 2023 ), taking place from April 14th to 19th at the Orange County Convention Center in Orlando, Florida, the United States. "The five posters we present at AACR 2023 provides Antengene with an opportunity to share a range of encouraging results including the expanded Phase II data of ATG-008 for the second-line treatment of patients with HBV+ HCC, as well as the preclinical results of ATG-017, ATG-037, ATG-031, and ATG-034,"said Dr. Bo Shan, Antengene's Chief Scientific Officer. "A highlight of the results is the promising tumor response and overall survival data from the study in patients with advanced disease as they suggest that ATG-008 monotherapy represent a promising therapeutic option for patients who have received prior systemic therapy, including PD-1/PD-L1 inhibitors. Maintaining our focus on addressing patients' unmet clinical needs, we will continue to actively explore and evaluate combinations between our existing programs and other targets and agents, with the hope of gathering sufficient rationale to support the future clinical development of these regimens." Details of the Poster Presentations: ATG-008 (mTORC1/2 inhibitor) Title: Result of an open-label phase 2 trial of dual TORC1/TORC2 inhibitor onatasertib(ATG-008) in HBV+ advanced hepatocellular carcinoma(HCC) subjects who have received at least one prior line of systemic therapy(TORCH) Abstract: CT150 Date: April 17, 2023 Time: 1:30 PM - 5:00 PM (Eastern Time) 1:30 AM - 5:00 AM, April 18, 2023 (Beijing Time) This Phase II study was designed to evaluate the pharmacokinetics, safety and efficacy of ATG-008 in patients with advanced hepatitis B virus (HBV) positive hepatocellular carcinoma (HCC). 73 patients with HBV+, unresectable and refractory HCC were enrolled to receive ATG-008 at one of the four dose levels. Data from this study showed that 3 subjects achieved a partial response ( PR ) , all in the 45 mg QD monotherapy cohort. A total of 18 patients were enrolled in this cohort that achieved an objective response rate (ORR) of 16.7%. Among them, 11 patients (61.1%) had received at least 2 prior lines of therapy and 15 patients had been exposed to an anti-PD-1/PD-L1 checkpoint inhibitor (CPI) (83.3%). The median progression-free survival (mPFS) was 3 months in the intend-to-treat (ITT) population and 5.3 months in the 45mg QD cohort. These data suggest that ATG-008 has single-agent efficacy in HBV+ HCC patients who have failed at least one prior systemic therapy, notably in the 45 mg QD dosing level, in which most patients had been previously exposed to an anti-PD-1/PD-L1 therapy. Further, the results indicate that ATG-008 has the potential in HBV+ HCC patients who have failed prior CPI therapy and support further study, particularly in patients who have failed prior anti-VEGF and anti-PD-l/PD-L1 therapy. ATG-008 is being evaluated in the Phase II TORCH-2 study in patients with cervical cancer and other solid tumors. ATG-017 (ERK1/2 inhibitor) T itle : Synergistic effects of the combination of ERK1/2 with EGFR, KRASG12C, CDK4/6, and PD-L1 inhibition for cancer treatment Abstract: 5499 Date: April 18, 2023 T ime : 1:30 PM – 5:00 PM (Eastern Time) 1:30 AM - 5:00 AM, April 19, 2023 (Beijing Time) This preclinical study was designed to test the in vivo anti-tumor effects induced by the combination of ATG-017, with EGFR inhibitor ( o simertinib), KRASG12C inhibitor (ATG-012), CDK4/6 inhibitor ( a bemaciclib) or PD-L1 inhibitor ( a tezolizumab), in preclinical tumor models including three models of non-small cell lung cancer (NSCLC) (with EGF-R and KRAS mutations), and one model of T-cell lymphoma (resistant to anti-PD-L1) for assessing the tumor growth inhibition (TGI) and the presence of tumor infiltrating lymphocytes (TILs). According to the results, ATG-017 demonstrated significant TGI (>60%) in the NSCLC models. In the T-cell lymphoma model, the combination of ATG-017 and the PD-L1 inhibitor, atezolizumab, showed significant tumor growth inhibition. Furthermore, that combination induced increased the infiltration of anti-tumor TILs, suggesting a potential role for ATG-017 in changing "cold" tumors to "hot". These data suggest that the combination of ATG-017 with EGFR, KRASG12C, CDK4/6, and PD-L1 inhibitors have strong synergism and significantly improved TGI, thus represent promising therapeutic strategies for cancer patients. Antengene is evaluating ATG-017 in the Phase I ERASER study, as monotherapy and in combination with nivolumab, in patients with advanced solid tumors and hematological malignancies in Australia and the U.S. ATG-037 (CD73 inhibitor) T itle : Targeting CD73-Adenosine Axis for the treatment of multiple myeloma Abstract: 496 Date: April 16, 2023 T ime : 1:30 PM – 5:00 PM (Eastern Time) 1:30 AM - 5:00 AM, April 17, 2023 (Beijing Time) This preclinical study was designed to evaluate the potential of ATG-037 in treating multiple myeloma (MM). CD73 is a cell surface enzyme which is highly expressed in the tumor microenvironment and enables the conversion of ATP to adenosine, promoting the progression of cancer by inhibiting T-cells, natural killer (NK) cells, and dendritic cells (DCs), and inducing and enhancing the function of immunosuppressive cell types. ATG-037's ability to inhibit the activity of CD73 was evaluated in enzyme inhibition and T cell proliferation and activation assays. In vivo efficacy was assessed in syngeneic myeloma models. Results showed complete inhibition of CD73 with ATG-037, without a "hook effect" compared to another industry benchmark antibody program. In addition, ATG-037 completely restored the function of activated T-cells and CAR-T cells from AMP-mediated T-cell suppression, suggesting a potential application in CAR-T cell therapy. In addition, the treatment with ATG-037 resulted in significant TGI compared to vehicle controls. These data suggest that ATG-037 has single agent anti-myeloma efficacy, thus making this abstract the first report of in vivo efficacy study of a CD73 inhibitors in myeloma animal models. Antengene is currently evaluating ATG-037 in Australia and mainland of China in the Phase I STAMINA study, as a monotherapy and in combination with pembrolizumab, in patients with locally advanced or metastatic solid tumors. ATG-031 (anti-CD24 monoclonal antibody) T itle : ATG-031, a first-in-class humanized anti-CD24 antibody, demonstrates potent in vivo efficacy and repolarizes tumor-associated macrophages in the TME Abstract: 6641 Date: April 19, 2023 Time: 9:00 AM – 12:30 PM (Eastern Time) 9:00 PM April 19 - 12:30 AM April 20, 2023 (Beijing Time) This preclinical study was designed to evaluate the in vivo efficacy of ATG-031 and explored its pharmacodynamic effects. Data showed that ATG-031 monotherapy produced robust, 60-100% TGI, with increased, synergistic tumor regression from the combination of ATG-031 with oxaliplatin (chemotherapy) or atezolizumab (CPI), evaluated in one of the murine models. Flow cytometry analysis shows that ATG-031 increases T cell (CD4/CD8) tumor infiltration and significantly lower population of Treg cells in the tumor microenvironment. These results suggest that the first-in-class antibody, ATG-031, specifically binds to CD24 with nM affinity and blocks the interaction of CD24 and Siglec-10. ATG-031 induces efficient phagocytosis with a picomolar EC50, stimulating pro-inflammatory cytokines production by macrophages. ATG-034 (LILRB4 antagonist antibody) T itle : ATG-034, an LILRB4 antagonist antibody, reinvigorates dendritic cells and prevents tumor progression Abstract: 6384 Date: April 19, 2023 T ime : 9:00 AM – 12:30 PM (Eastern Time) 9:00 PM April 19 - 12:30 AM April 20, 2023 (Beijing Time) This preclinical study was designed to evaluate ATG-034, an antibody targeting LILRB4, as a potential immunotherapy . The antibody was tested using SPR, ELISA and FACS analysis to assess its ability to bind to LILRB4, block its interaction with its ligand, fibronectin, and reinvigorate DCs to an "immunogenic" state. According to the data, ATG-034 demonstrated single-digit nanomolar affinity and blocked the interaction of LILRB4 with its target ligand, fibronectin and completely reversed fibronectin-mediated suppression of tolerized DC activation (TolDC), evidenced by increased TNF-a production. In addition, the antibody reprogrammed DCs to become immunogenic, as measured by the up regulation of several key co-stimulatory molecules (CD86, HLA-DR and HLA-ABC) and down-regulation of an M2 biomarker (CD206). These results suggest that ATG-034 successfully reprogrammed tolerized DCs to an "immunogenic" state, thereby enhancing anti-tumor immunity and demonstrating potent in vivo anti-tumor efficacy compared to a benchmarking compound . About Antengene Antengene Corporation Limited ( "Antengene", SEHK: 6996.HK) is a leading commercial-stage R&D-driven global biopharmaceutical company focused on the discovery, development, manufacturing and commercialization of innovative first-in-class/best-in-class therapeutics for the treatment of hematologic malignancies and solid tumors, in realizing its vision of "Treating Patients Beyond Borders". Since 2017, Antengene has built a pipeline of 9 oncology assets at various stages going from clinical to commercial, including 6 with global rights, and 3 with rights for the APAC region. To date, Antengene has obtained 28 investigational new drug (IND) approvals in the U.S. and Asia, and submitted 9 new drug applications (NDAs) in multiple Asia Pacific markets, with the NDA for XPOVIO® (selinexor) already approved in Mainland of China, Taiwan,China, South Korea, Singapore and Australia. Forward-looking statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. For a further discussion of these and other factors that could cause future results to differ materially from any forward-looking statement, see the section titled "Risk Factors" in our periodic reports filed with the Hong Kong Stock Exchange and the other risks and uncertainties described in the Company's Annual Report for year-end December 31, 2021, and subsequent filings with the Hong Kong Stock Exchange. For more information, please contact: Investor Contacts: Donald Lung E-mail: [email protected] Mobile: +86 18420672158 PR Contacts: Peter Qian E-mail: [email protected] Mobile: +86 13062747000 SOURCE Antengene Corporation Limited

CHICAGO & SHANGHAI--(BUSINESS WIRE)-- JS InnoPharm Ltd initiated the JSI-1187 plus dabrafenib combination dose-escalation phase of the Phase 1 study for patients with locally advanced or metastatic solid tumors with confirmed BRAF V600E/K mutations (NCT04418167). The clinical study is being conducted at 8 NCI-designated Comprehensive Cancer Centers in the U.S. JSI-1187 is a potent, orally active ERK1 and ERK2 inhibitor. JS InnoPharm holds the U.S. IND for JSI-1187, and this trial is being managed by Strategia Pharmaceuticals LLC, JS InnoPharm’s clinical development partner in the United States. The JSI-1187 monotherapy dose escalation phase of this study was initiated in 2020 for the treatment of patients with relapsed or refractory, locally advanced or metastatic solid tumors with MAPK pathway mutations, including hyperactivating mutations or gene fusions. “JSI-1187 is a selective ERK1/2 inhibitor. By utilizing an ERK inhibitor against tumors harboring mutations in the MAPK pathway, we hope to develop more effective single-agent and combination therapies by preventing the early development of resistance seen with current MAPK targeted agents,” said Dr. Linda Paradiso, Chief Development Officer for Strategia Pharmaceuticals. “Our preclinical studies have demonstrated significant potential of JSI-1187 in combination with dabrafenib, and we are excited to initiate the ERK/BRAF combination treatment at these important clinical cancer sites in the US,” said Dr. Jintao Zhang, Chief Executive Officer for JS InnoPharm. The Role of ERK in Cancer MAPK signaling via the RAS-RAF-MEK-ERK pathway plays a critical role in cancer growth and proliferation. Alterations in the MAPK-ERK pathway are found in a variety of cancer types, including KRAS mutations in pancreatic (>90%), biliary tract (3-50%), colorectal (30-50%), lung (25-30%), ovarian (15-39%) and endometrial (18%) cancers; NRAS mutations in melanoma (20%); BRAF V600 mutations in melanoma (50%) and a variety of other tumor types (7% overall). BRAF/MEK inhibitor combination therapy provides a significant benefit beyond single agent therapy in melanoma and other cancers. However, many patients don’t respond to the combination therapy and most responding patients eventually develop acquired resistance and disease progression. Several mechanisms of acquired resistance have been identified and the reactivation of ERK signaling is central to these mechanisms. Therefore, a combination of ERK inhibition with JSI-1187 and dabrafenib may provide a targeted approach to delay or overcome resistance, as ERK is the most distal kinase of the MAPK signaling pathway. About JSI-1187 JSI-1187 is a selective and orally administered small molecule inhibitor of ERK1 and ERK2. In preclinical studies, JSI-1187 demonstrated high potency against a variety of tumors with MAPK pathway mutations. About JS InnoPharm Ltd JS InnoPharm is a clinical stage biopharmaceutical company, dedicated to the discovery and development of novel chemical entities for cancer therapy, leveraging cutting edge knowledge in mutations, biomarkers, and precision medicine. JS InnoPharm is building an innovative pipeline by internal R&D as well as global partnering and licensing, and developing multiple clinical candidates with differential clinical strategies.

Promising preliminary monotherapy data for ERK1/2 inhibitor ERAS-007 and SHP2 inhibitor ERAS-601 in advanced solid tumors, which had favorable safety, tolerability, and efficacy profiles that support combination development BRAF Class 2 and 3 alterations have no approved targeted therapies and represent up to 25% of all BRAF-driven tumors SAN DIEGO, CA, USA I December 20, 2022 I Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, today announced dosing of the first patient in the HERKULES-1 Phase 1b trial evaluating ERK1/2 inhibitor ERAS-007 in combination with SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in patients with RAS/MAPK pathway-altered solid tumors. “We are pleased with our team’s efficient execution that resulted in dosing the first patient in our MAPKlamp trial in 2022 ahead of schedule,” said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. “ERK and SHP2 inhibition with ERAS-007 and ERAS-601 targets critical downstream and upstream nodes in the RAS/MAPK pathway, offering a rational approach that is supported by early clinical data that we presented at our R&D Day in September. Notably, we reported four responses in nine patients with BRAF-driven tumors to either monotherapy ERAS-007 or ERAS-601. Three of these responses were in tumors with BRAF Class 2 or 3 alterations, including a confirmed response to monotherapy SHP2 inhibition in a patient with a BRAF Class 3 alteration, which is dependent on upstream receptor tyrosine kinase (RTK) activation. We look forward to exploring the potential to address the high unmet need in these BRAF subtypes, which have no approved targeted therapies and represent up to 25% of all BRAF-driven tumors.” The MAPKlamp portion of HERKULES-1 will initially examine the safety, tolerability, and preliminary efficacy of ERAS-007 in combination with ERAS-601 in patients with RAS/MAPK pathway-altered solid tumors. After a recommended dose is determined, the Phase 2 expansion portion will further evaluate the safety and efficacy of the combination in patients with different mutational subtypes, including BRAF Class 2 and 3 patients. ERAS-007 and ERAS-601 had favorable monotherapy safety and tolerability profiles with largely non-overlapping treatment-related adverse events that support combination development. Forty-four percent (4/9) of patients with BRAF-driven tumors responded (one confirmed and three unconfirmed PRs) to single agent ERAS-007 or ERAS-601, including three (one confirmed and two unconfirmed PRs) in tumors with BRAF Class 2 and 3 alterations. The clinical data referred to above was presented at Erasca’s September 7, 2022 R&D Day, and consisted of a retrospective pooled interim analysis of monotherapy ERAS-007 and ERAS-601 data, with data cutoff dates of 11/6/20, 7/11/22, and 5/16/22 for the ASN007-101, FLAGSHP-1, and HERKULES-1 trials, respectively. About ERAS-007 ERAS-007 is a potential best-in-class ERK1/2 inhibitor being investigated alone or in combination with different inhibitors targeting upstream nodes of the RAS/MAPK pathway as part of Erasca’s MAPKlamp strategy. The extracellular signal-regulated kinases (ERK), ERK1 and ERK2, belong to a family of serine-threonine kinases that regulate cellular signaling and comprise the terminal node of the RAS/MAPK pathway. ERAS-007 is being investigated across the series of HERKULES clinical trials that span multiple tumor types and includes both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, RAF, and/or cell cycle inhibitors. HERKULES-1 is a Phase 1b/2 clinical trial for ERAS-007 as a single agent and in combination with the SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in advanced solid tumors. HERKULES-2 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with non-small cell lung cancer (NSCLC). HERKULES-3 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with gastrointestinal (GI) cancers. About ERAS-601 ERAS-601 is a potential best-in-class oral, selective SHP2 inhibitor being investigated alone or in combination. SHP2 acts as a convergent node for receptor tyrosine kinase (RTK) signaling, relaying growth and survival signals from RTKs to intracellular signaling pathways. ERAS-601 combined with the ERK1/2 inhibitor ERAS-007 makes up Erasca’s first innovative MAPKlamp strategy. ERAS-601 is being investigated across a series of clinical trials that span multiple tumor types and include both monotherapy and combinations with approved and investigational agents. FLAGSHP-1 is a Phase 1/1b clinical trial evaluating ERAS-601 as a monotherapy in advanced solid tumors and in combination in triple wildtype (KRAS/NRAS/BRAF wildtype) CRC and human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). HERKULES-1 is a Phase 1b/2 clinical trial that includes evaluation of ERAS-601 in combination with ERAS-007 in advanced solid tumors. HERKULES-2 is a Phase 1b/2 master protocol clinical trial that includes evaluation of ERAS-601 in combination with various agents in patients with non-small cell lung cancer (NSCLC). About Erasca At Erasca, our name is our mission: To eras e ca ncer. We are a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers. Our company was co-founded by leading pioneers in precision oncology and RAS targeting to create novel therapies and combination regimens designed to comprehensively shut down the RAS/MAPK pathway for the treatment of cancer. We have assembled what we believe to be the deepest RAS/MAPK pathway-focused pipeline in the industry. We believe our team’s capabilities and experience, further guided by our scientific advisory board which includes the world’s leading experts in the RAS/MAPK pathway, uniquely position us to achieve our bold mission of erasing cancer. SOURCE: Erasca