Lodapolimab

First three out of five cohorts pass safety requirements, allowing the Company to dose additional cohorts to assess safety, tolerability, pharmacokinetics and anti-tumor activity HONG KONG, GERMANTOWN, Md., and SUZHOU, China, Dec. 20, 2022 /PRNewswire/ -- Sirnaomics Ltd. (Stock Code: 2257.HK) (the " Company", together with its subsidiaries, " Sirnaomics" or the " Group"), a leading biopharmaceutical company in discovery and development of RNAi therapeutics, announced today the interim results from a Phase I clinical trial evaluating the safety, tolerability and anti-tumor activity of the Company's siRNA (small interfering RNA) drug candidate, STP707 with intravenous (IV) administration in the United States. This is a basket study which enrolls various solid tumor types. The analysis included the first three cohorts in a five-cohort dose escalation study. The multi-center, open label, dose escalation and dose expansion tumor basket study evaluates the safety, tolerability and anti-tumor activity of STP707. Twenty participants with advanced solid tumors, who have been unresponsive to standard therapies, are included in the dose escalation analysis. Once maximum tolerated dose or recommended Phase II dose has been established, additional patients will be enrolled to confirm safety and explore anti-tumor activity. The study encompasses five total cohorts who will receive escalating doses of STP707 through IV administration on a 28-day cycle including 3 mg, 6 mg, 12 mg, 24 mg and 48 mg dosing cohorts. The interim analysis involves subjects from the 3 mg, 6 mg, and 12 mg dosing cohorts. The subjects were dosed once per week for a total of 4 doses over a 28-day treatment cycle and will continue to be dosed in the study until they exhibit progressive disease. Additional secondary endpoints are to determine the pharmacokinetics of STP707 and to observe preliminary anti-tumor activity. This interim data is from the first three cohorts treated with three different doses of STP707. "We are very excited to see STP707, our leading siRNA drug product for treatment of multiple solid tumors through an intravenous administration in which the first three cohorts with twenty patients have been completed showing strong safety profile and efficacy readouts. This is the first time that an RNAi (RNA interference) cancer therapeutic has demonstrated a very promising clinical potential for metastasized tumors. The interim data of STP707 will allow us to expand our research with additional cohorts — a positive step forward in moving this treatment into the next phase," said Dr. Patrick Lu, Founder, Chairman of the Board, Executive Director, President and CEO of Sirnaomics. "This Phase I basket clinical study result encourages us to proceed to a potential combination study with immune check point inhibitor drugs. We look forward to expanding clinical trials with STP707 that has the potential to address the unmet needs of patients with solid tumors and other cancers." "The progress of our dose escalation STP707 solid tumor basket study is a significant milestone as we seek to advance this novel siRNA oncology therapeutic," said Dr. Michael Molyneaux, M.D., Executive Director and Chief Medical Officer of Sirnaomics. "We have passed each of the first three cohorts' safety requirements for dose escalation and anticipate dosing our fourth cohort in the first quarter 2023. To date, STP707 has exhibited a strong safety profile when compared to other novel oncology therapeutics." Dr. Molyneaux added, "The 20 subject data set demonstrates an encouraging efficacy signal with duration of response equal to or exceeding two treatment cycles or 56 days in 8 subjects examined over all dosing cohorts. There have also been a number of tumor types including liver, pancreatic, colon and uveal melanoma cancers that have exhibited stable disease beyond 100 days of treatment. It is important to emphasize the fact that the subjects in this study have received multiple forms of prior treatments including surgery, radiation, and tumor specific first- and second-line therapies. As all subjects demonstrated progressive disease on prior treatment regimens, this group of subjects represents a subset of resistant tumor types that have not responded to all prior therapies. It is encouraging to see very good safety combined with duration of response in such resistant tumor types, and we look forward to continuing this study." STP707 takes advantage of a dual-targeted inhibitory property and a PNP-enhanced targeted delivery to solid tumors and metastatic tumors via intravenous administration. An initial preclinical study has demonstrated that simultaneously knocking down TGF-β1 and COX-2 gene expression in the tumor microenvironment increases active T cell infiltration. A further combination study demonstrated synergistic anti-tumor activity between STP707 and a PD-L1 antibody using a mouse orthotopic liver cancer model. For more information about Sirnaomics' clinical trials, please visit ClinicalTrials.gov (Identifier NCT05037149) and the Company's website at . About STP707 STP707 is composed of two siRNA oligonucleotides, targeting TGF-β1 and COX-2 mRNA respectively, formulated in nanoparticles with a Histidine-Lysine Co-Polymer (HKP+H) peptide as the carrier. The specific carrier peptide is distinct from the carrier used in Sirnaomics' sTP705 product. Each individual siRNA was demonstrated to inhibit the expression of their target mRNAs and combining the two siRNA's produces a synergistic effect that diminishes pro-inflammatory factors. Over-expression of TGF-β1 and COX-2 have been well-characterized in playing key regulatory roles in tumorigenesis. In preclinical studies with STP707, IV administration resulted in knock-down of TGF-β1 and COX-2 gene expressions in various organs including liver, lung and xenograft tumor. In addition, in preclinical models STP707 had shown strong anti-tumor activity in various solid tumor types. Using a mouse liver orthotopic tumor model, a combination regimen of STP707 with an immune checkpoint antibody has demonstrated a potent anti-tumor activity. About Sirnaomics Sirnaomics is an RNA therapeutics biopharmaceutical company with product candidates in preclinical and clinical stages that focuses on the discovery and development of innovative drugs for indications with medical needs and large market opportunities. Sirnaomics is the first clinical-stage RNA therapeutics company to have a strong presence in both China and the United States, and also the first company to achieve positive Phase IIa clinical outcomes in oncology for an RNAi therapeutics for its core product, STP705. Learn more at . CONTACT: Michael Molyneaux, M.D., MBA Executive Director and Chief Medical Officer, Sirnaomics Email: [email protected] Investor Relations: Nigel Yip, MBA Chief Financial Officer, Sirnaomics Email: [email protected] US Media Contact: Alexis Feinberg Tel: +1 203 939 2225 Email: [email protected] Asia Media Contact: Bunny Lee Tel: +852 3150 6707 Email: [email protected] SOURCE Sirnaomics Ltd.

Adagrasib in combination with pembrolizumab demonstrates favorable tolerability and promising preliminary efficacy in patients with first-line advanced/metastatic NSCLC harboring a KRASG12C mutation Findings will be presented on December 7 at the 2022 ESMO Immuno-Oncology Annual Congress, as an oral presentation from 2:05 p.m.-2:15 p.m. CET / 8:05 a.m.-8:15 a.m. ET (Presentation #LBA4) during the "Proffered Paper session 1" session. SAN DIEGO, Dec. 5, 2022 /PRNewswire/ -- Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage oncology company today announced preliminary results from the KRYSTAL-7 Phase 2 trial and KRYSTAL-1 Phase 1b cohort evaluating adagrasib (400mg twice daily) concurrently combined with pembrolizumab in patients for the treatment of first-line NSCLC harboring a KRASG12C mutation across all PD-L1 subgroups. These data are the first to demonstrate the tolerability and feasibility of a concurrent combination regimen of a KRASG12C inhibitor and a PD-1/L1 checkpoint inhibitor. Summary of Clinical Results The KRYSTAL-7 and KRYSTAL-1 trials represent the largest dataset evaluating a KRASG12C inhibitor in combination with a PD-1/L1 checkpoint inhibitor as a first-line treatment for patients with NSCLC harboring a KRASG12C mutation. 75 patients were enrolled and evaluable for safety with a median follow-up of 3.5 months (duration of treatment: 2 months). Treatment-related adverse events (TRAEs) were Grade 1-2 (39%), Grade 3 (40%) and Grade 4 (4%); there were no Grade 5 TRAEs observed. TRAEs led to discontinuation of both adagrasib and pembrolizumab in 2 patients and only pembrolizumab in 2 patients; there were no patients who discontinued only adagrasib due to a TRAE. Increases in alanine transaminase (ALT)/ aspartate transaminase (AST) were consistent with either agent as a monotherapy with Grade 3 TRAEs being highest grade and total incidence of Grade 3 liver function test (LFT) increases of 9%. Median time from onset to an increase in ALT and AST was 26 and 37 days, respectively and only 1 patient experienced new onset treatment-related ALT/AST increase after 3 months. Of patients who were clinically evaluable and received at least one on-study scan (n=53), adagrasib and pembrolizumab demonstrated promising preliminary clinical activity across all PD-L1 subgroups with an objective response rate (ORR) of 49%. In a subset of response-evaluable patients enrolled at least 6 months prior to the data cutoff date, 6 of 26 clinical responses occurred at second on-study scan or later, and the ORR was 56%. 7 evaluable patients enrolled in the KRYSTAL-1 Phase 1b cohort (with a median follow-up of 19.3 months) reported an ORR of 57% and a disease control rate (DCR) of 100%. The four patients who responded maintained response for over nine months while two continued to receive treatment and remain in response beyond 18 months. Safety in the KRYSTAL-1 Phase 1b cohort was consistent with what has been observed in KRSTYAL-7 and demonstrated a manageable safety profile with no Grade 4-5 TRAEs. "Initial results across all cohorts suggest the concurrent combination of adagrasib and pembrolizumab may provide a chemotherapy-free option for treatment-naïve NSCLC with a manageable safety profile and encouraging clinical activity," said Pasi A. Jänne, MD, PhD, Dana Farber Cancer Institute. "Across all evaluated cohorts, liver-related TRAEs were predominantly low grade and occurred early in treatment, with limited new onset after 3 months." "We look forward to progressing our clinical development in the first line setting with a goal of providing better options for patients with NSCLC harboring a KRASG12C mutation," said Chuck Baum, president, founder, and head of research and development, Mirati Therapeutics, Inc. "This data further underscores the potential of adagrasib as a well-tolerated treatment option for patients. Based on these data, we look forward to initiating a Phase 3 trial." The data (Presentation #LBA4) will be presented in an oral presentation on Dec. 7 at 2:05 p.m.-2:15 p.m. CET / 8:05 a.m.-8:15 a.m. ET during the Proffered Paper session 1 at the European Society for Medical Oncology Immuno-Oncology (ESMO IO) Congress 2022. Virtual Investor Event Mirati Therapeutics will host an Investor Event on Wednesday, December 7, 2022, at 5:00 p.m. CET / 11:00 a.m. ET. Company executives will provide an overview of the adagrasib and pembrolizumab combination data presented 2022 ESMO Immuno-Oncology Annual Congress. Investors and the general public are invited to register and listen to a live webcast of the event through the "Investors and Media" section on Mirati.com. A replay of the event will be available shortly after the conclusion of the event. About Adagrasib (MRTX849) Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24-48 hours. Studies of adagrasib have shown that the drug has a long half-life and extensive tissue distribution, and is well tolerated. In clinical trials, adagrasib also has shown, central nervous system penetrance and single-agent responses in non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer and other solid tumors with KRASG12C mutations. Adagrasib is being evaluated in several clinical trials in combination with other anti-cancer therapies in patients with advanced solid tumors. Registration-enabling studies are ongoing in NSCLC and colorectal cancer. For more information visit Mirati.com/science. About Mirati Therapeutics, Inc. Mirati Therapeutics, Inc. is a biotechnology company whose mission is to discover, design and deliver breakthrough therapies to transform the lives of patients with cancer and their loved ones. The company is relentlessly focused on bringing forward therapies that address areas of high unmet need, including lung cancer, and advancing a pipeline of novel therapeutics targeting the genetic and immunological drivers of cancer. Unified for patients, Mirati's vision is to unlock the science behind the promise of a life beyond cancer. For more information about Mirati, visit us at Mirati.com or follow us on Twitter, LinkedIn and Facebook. Forward Looking Statements This press release contains forward-looking statements regarding the business of Mirati Therapeutics, Inc. ("Mirati"). Any statement describing Mirati's goals, expectations, financial or other projections, intentions or beliefs, development plans and the commercial potential of Mirati's drug development pipeline, including without limitation adagrasib (selective KRASG12C inhibitor), sitravatinib (TAM receptor inhibitor), MRTX1719 (MTA-cooperative PRMT5 inhibitor), MRTX0902 (SOS1 inhibitor), and MRTX1133 (selective KRASG12D inhibitor), is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to risks and uncertainties, particularly those challenges inherent in the process of discovering, developing and commercialization of new drug products that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Mirati's forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Mirati's forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Mirati. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Mirati's programs are described in additional detail in Mirati's quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the U.S. Securities and Exchange Commission (the "SEC") available at the SEC's Internet site (). These forward-looking statements are made as of the date of this press release, and Mirati assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Mirati Contacts Investor Relations: [email protected] Media Relations: [email protected] References 1 Hallin J, Engstrom LD, Hargis L, et al. The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients. Cancer Discov. 2020;10(1):54-71. SOURCE Mirati Therapeutics, Inc.