Paclitaxel

— Third major market authorization application based on data from the FRESCO-2 global Phase III trial —HONG KONG and SHANGHAI, China and FLORHAM PARK, N.J., Sept. 29, 2023 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (Nasdaq/AIM:​HCM, HKEX:​13) (“HUTCHMED”) today announced that Takeda (TSE:4502/​NYSE:TAK) has submitted a New Drug Application (“NDA”) to the Ministry of Health, Labour and Welfare (“MHLW”) in Japan for the approval of fruquintinib for the treatment of adult patients with previously treated metastatic colorectal cancer (“CRC”). Fruquintinib is a selective inhibitor of vascular endothelial growth factor receptors (“VEGFR”) -1, -2 and -3, which play a pivotal role in blocking tumor angiogenesis. CRC has the highest incidence and second highest mortality rate among both men and women in Japan.1 The NDA for fruquintinib is based on results from FRESCO-2, a global Phase III multi-regional clinical trial (MRCT) conducted in the U.S., Europe, Japan and Australia, as well as data from the Phase III FRESCO clinical trial conducted in China. The FRESCO-2 and FRESCO clinical trials compared fruquintinib plus best supportive care (“BSC”) with placebo plus BSC in patients with previously treated metastatic CRC. Both trials met their primary and key secondary endpoints, showing a statistically significant and clinically meaningful improvement in overall survival (“OS”) and progression-free survival (“PFS”). Fruquintinib has been generally well tolerated by patients. “Alongside our partner Takeda, we are pleased to take this key step towards bringing fruquintinib to patients in Japan,” said Dr. Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED. “Supported by a strong clinical data set, and its success in China, we believe that fruquintinib is an important option for these patients and are optimistic about the impact it will have if approved in Japan. There is now real regulatory momentum behind fruquintinib, and we are excited to see this drug take to the global stage.” This submission follows prior submissions for fruquintinib in the U.S. and Europe for the same indication. The U.S. Food and Drug Administration (“FDA”) granted Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of November 30, 2023. The FDA review is progressing and the inspection of HUTCHMED’s manufacturing facility in Suzhou, China has been completed. A Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) was validated and accepted for regulatory review in June 2023. Data from the global registrational FRESCO-2 clinical trial was published in The Lancet, also in June 2023 (NCT04322539).2 Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of China. Fruquintinib is developed and marketed in China by HUTCHMED, under the brand name ELUNATE®. Approval in China was based on the results of the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, published in The Journal of the American Medical Association, JAMA (NCT02314819).3 About Fruquintinib Fruquintinib is a selective oral inhibitor of VEGFR -1, -2 and -3. VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for the potential use as part of combination therapy. Fruquintinib has been shown to be generally well tolerated in patients to date. About FRESCO-2 The FRESCO-2 study is a multi-regional clinical trial conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus BSC vs placebo plus BSC in patients with previously treated metastatic CRC. As previously disclosed, the 691-patient study met its primary endpoint of OS in patients with metastatic CRC who had progressed on standard chemotherapy and relevant biologic agents and who had progressed on, or were intolerant to, TAS-102 and/or regorafenib. In addition to OS, a statistically significant improvement in PFS, a key secondary endpoint, was observed. Fruquintinib has been generally well tolerated in patients to date. Results were presented at the European Society for Medical Oncology (ESMO) Congress in September 2022 and subsequently published in The Lancet.4 Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04322539. About CRC CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer, CRC is the third most prevalent cancer worldwide, associated with more than 935,000 deaths in 2020.5 In the U.S., it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2023.6 In Europe, CRC was the second most common cancer in 2020 with approximately 520,000 new cases and 245,000 deaths. In Japan, CRC was the most common cancer with an estimated 148,000 new cases and 60,000 deaths in 2020.5 Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.7,8,9,10,11 About HUTCHMED HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three oncology drugs now approved and marketed in China. For more information, please visit: www.hutch-med.com or follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the approval of a NDA for fruquintinib for the treatment of CRC with the FDA, EMA and the MHLW and the timing of such approvals, the therapeutic potential of fruquintinib for the treatment of patients with CRC and the further clinical development of fruquintinib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the timing and outcome of clinical studies and the sufficiency of clinical data to support NDA approval of fruquintinib for the treatment of patients with CRC or other indications in Japan or other jurisdictions such as the U.S. or the E.U., its potential to gain approvals from regulatory authorities on an expedited basis or at all; the efficacy and safety profile of fruquintinib; HUTCHMED and/or Takeda’s ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib; the timing of these events; each party’s ability to satisfy the terms and conditions under the license agreement; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or the regulatory pathway for fruquintinib; Takeda’s ability to successfully develop, manufacture and commercialize fruquintinib; and the impact of COVID-19 on general economic, regulatory and political conditions. In addition, as certain studies rely on the use of other drug products such as paclitaxel as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Such forward-looking statements include, without limitation, statements regarding the plan to develop, manufacture and commercialize fruquintinib under the license agreement; potential payments under the license agreement, including the upfront payment and any milestone or royalty payments; potential benefits of the license agreement; and HUTCHMED’s strategy, goals and anticipated milestones, business plans and focus. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and on The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. Medical Information This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. CONTACTS Investor Enquiries+852 2121 8200 / +1 973 306 4490 / ir@hutch-med.com Media Enquiries Ben Atwell / Alex Shaw, FTI Consulting+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) / HUTCHMED@fticonsulting.comZhou Yi, Brunswick+852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com Nominated Advisor Atholl Tweedie / Freddy Crossley / Daphne Zhang, Panmure Gordon+44 (20) 7886 2500 _____________________________ 1 Cancer Statistics. Cancer Information Service, National Cancer Center, Japan (Vital Statistics of Japan, Ministry of Health, Labour and Welfare). https://ganjoho.jp/public/qa_links/report/statistics/2023_jp.html.2 Dasari NA, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study [published online ahead of print, 2023 Jun 15]. Lancet. 2023. DOI: 10.1016/S0140-6736(23)00772-9.3 Li J, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486-2496. doi:10.1001/jama.2018.7855.4 Dasari NA, et al. LBA25 – FRESCO-2: A global phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Ann Oncol. 2022 Sep;33(suppl_7): S808-S869. doi:10.1016/annonc/annonc1089.5 Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660.6 Siegel RL, et al. Colorectal cancer statistics, 2023 [published online ahead of print, 2023 Mar 1]. CA Cancer J Clin. 2023; 73(3):233-254. doi:10.3322/caac.21772.7 Bando H, et al. Therapeutic landscape and future direction of metastatic colorectal cancer. Nat Rev Gastroenterol Hepatol. 2023;20(5):306-322. doi:10.1038/s41575-022-00736-1.8 D'Haene N, et al. Clinical application of targeted next-generation sequencing for colorectal cancer patients: a multicentric Belgian experience. Oncotarget. 2018;9(29):20761-20768. Published 2018 Apr 17. doi:10.18632/oncotarget.25099.9 Venderbosch, et al. Mismatch repair status and braf mutation status in metastatic colorectal cancer patients: A pooled analysis of the Cairo, Cairo2, coin, and Focus Studies. Clinical Cancer Res. 2014;20(20):5322–5330. doi:10.1158/1078-0432.ccr-14-0332. 10 Koopman, M., et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer. 2009;100(2):266–273. doi:10.1038/sj.bjc.6604867.11 Ahcene Djaballah S, et al. HER2 in Colorectal Cancer: The Long and Winding Road From Negative Predictive Factor to Positive Actionable Target. Am Soc Clin Oncol Educ Book. 2022;42:1-14. doi:10.1200/EDBK_351354.

Intent-to-treat population shows 9-month OS improvement over control arm Subgroup of patients treated with IMNN-001 + PARPi shows meaningful PFS and OS trend compared with control arm Continued follow-up is indicated to confirm initial observations LAWRENCEVILLE, N.J., Sept. 28, 2023 (GLOBE NEWSWIRE) -- IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage biotechnology company focused on developing DNA-mediated immunotherapies and next-generation vaccines, announces interim progression-free survival (PFS) and overall survival (OS) data with IMNN-001 in its Phase 1/2 OVATION 2 Study. IMNN-001 is the Company’s IL-12 gene-mediated immunotherapy based on its TheraPlas™ technology. Full enrollment of 110 patients was reached in September 2022. OVATION 2 is evaluating the dosing, safety, efficacy and biological activity of intraperitoneal IMNN-001 in combination with neoadjuvant chemotherapy (NACT) in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. NACT is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of chemotherapy to treat any residual tumor. As expected for a Phase 1/2 study, the study is directional and was designed with an 80% confidence interval to show an approximate 33% improvement in PFS, when comparing the treatment arm (NACT + IMNN-001) with the control arm (NACT only). The secondary endpoints include OS, objective response rate (ORR), pathological response, surgical response and serologic response. The study was not powered for p values of 0.05. The final readout of this study is expected by mid-2024. A positive readout would inform next development steps. Interim data from the intent-to-treat (ITT) population being reported today show efficacy trends in PFS, demonstrating a delay in disease progression in the treatment arm of approximately 33% compared with the control arm, with the hazard ratio nearing the required value. Preliminary OS data follows a similar trend, showing an approximate 9-month improvement in the treatment arm over the control arm. Subgroup analyses show patients treated with a PARP inhibitor (PARPi) as maintenance therapy had longer PFS and OS if they were also treated with IMNN-001 compared with patients treated with NACT only. This was not a pre-specified subgroup as PARP inhibitors were approved after the OVATION 2 Study was initiated. The median PFS in the PARPi + NACT group and the PARPi + NACT + IMNN-001 group was 15.7 months and 23.7 months, respectively.The median OS in the PARPi + NACT group was 45.6 months and has not yet been reached in the PARPi + NACT + IMNN-001 group. While the data is still preliminary, the Company has concluded at this point that patients treated with a combination of NACT + PARPi + IMNN-001 appear to have the greatest benefit and should be the focus of on-going follow up. IMUNON also continues to see benefits in other secondary endpoints including an approximately 20% higher R0 tumor resection score and a doubling of the CRS 3 chemotherapy response score to approximately 30% in the treatment arm versus 14% in the control arm. A complete tumor resection (R0) is a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed. Chemotherapy response score is considered a good prognostic indicator in ovarian cancer. Safety analyses continue to show good tolerability of IMNN-001 in this setting. Commenting on the interim data, Dr. Corinne Le Goff, IMUNON’s president and chief executive officer, said, “We are encouraged by these interim results and are particularly intrigued by the overall survival trends in the subgroup of patients who received PARP inhibitors, neoadjuvant chemotherapy and IMNN-001. While the number of patients in this subgroup is relatively small, this regimen may hold potential in treatment strategies as we continue to monitor patients enrolled in OVATION 2, with expectations to report topline results in mid-2024.” About IMNN-001 Immunotherapy Designed using IMUNON's proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. The Company previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer, and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer. About Epithelial Ovarian Cancer Epithelial ovarian cancer (EOC) is the fifth deadliest malignancy among women in the United States. There are approximately 22,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced Stage III/IV. EOC is characterized by dissemination of tumor in the peritoneal cavity with a high risk of recurrence (75% in Stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with Stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate, but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation. About IMUNON IMUNON is a fully integrated, clinical-stage biotechnology company focused on advancing a portfolio of innovative treatments that harness the body’s natural mechanisms to generate safe, effective and durable responses across a broad array of human diseases, constituting a differentiating approach from conventional therapies. IMUNON is developing its non-viral DNA technology across four modalities. The first modality, TheraPlas™, is developed for the coding of proteins and cytokines in the treatment of solid tumors where an immunological approach is deemed promising. The second modality, PlaCCine™, is developed for the coding of viral antigens that can elicit a strong immunological response. This technology may represent a promising platform for the development of vaccines in infectious diseases. The third modality, FixPlas™, concerns the application of our DNA technology to produce universal cancer vaccines, also called tumor-associated antigen cancer vaccines. The fourth modality, which is in the discovery phase, IndiPlas™, will focus on the development of personalized cancer vaccines, or neoepitope cancer vaccines. The Company’s lead clinical program, IMNN-001, is a DNA-based immunotherapy for the localized treatment of advanced ovarian cancer currently in Phase 2 development. IMNN-001 works by instructing the body to produce safe and durable levels of powerful cancer-fighting molecules, such as interleukin-12 and interferon gamma, at the tumor site. Additionally, the Company is conducting IND-enabling preclinical studies for the development of a COVID-19 booster vaccine (IMNN-101) and a treatment for the Lassa virus (IMNN-102). The Company has also initiated preclinical work to develop a Trp2 tumor-associated antigen cancer vaccine in melanoma: IMNN-201. We will continue to leverage these modalities and to advance the technological frontier of plasmid DNA to better serve patients with difficult-to-treat conditions. For more information on IMUNON, visit www.imunon.com. Forward-Looking Statements IMUNON wishes to inform readers that forward-looking statements in this news release are made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Readers are cautioned that such forward-looking statements involve risks and uncertainties including, without limitation, unforeseen changes in the course of research and development activities and in clinical trials; the uncertainties of and difficulties in analyzing interim clinical data; the significant expense, time and risk of failure of conducting clinical trials; the need for IMUNON to evaluate its future development plans; possible acquisitions or licenses of other technologies, assets or businesses; possible actions by customers, suppliers, competitors or regulatory authorities; and other risks detailed from time to time in IMUNON’s periodic reports and prospectuses filed with the Securities and Exchange Commission. IMUNON assumes no obligation to update or supplement forward-looking statements that become untrue because of subsequent events, new information or otherwise. Contacts: IMUNONLHA Investor RelationsJeffrey W. ChurchKim Sutton GolodetzExecutive Vice President, CFO212-838-3777609-482-2455Kgolodetz@lhai.comjchurch@imunon.com # # #