Sotorasib

New KRAS-mutant data show ATNM-400 outperformed standard-of-care inhibitors sotorasib and adagrasib as a monotherapy. Treatment with these agents increased expression of the ATNM-400 target greater than 3.5x and enhanced their effect in combination Additional data in the EGFR-mutant setting demonstrated powerful synergy with osimertinib due to enhanced target expression in treated animals resulting in complete tumor regression in the combination arm The data with EGFR and KRAS mutations which account for approximately 40-50 percent of all NSCLC cases provide compelling evidence of the potential of ATNM-400 as a monotherapy or in combination with inhibitory agents against these mutations ATNM-400 is a radioconjgate comprising an antibody coupled to Actinium-225 which causes cell death via double stranded DNA breaks independent of cellular mechanisms and offers broad potential as a mutation agnostic agent in NSCLC where its target is expressed in over 90 percent of tumors with greater expression as resistance emerges NEW YORK, June 3, 2026 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE American: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, on June 2, 2026, presented new preclinical data on ATNM-400 in non-small cell lung cancer (NSCLC) at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2026 Annual Meeting in Los Angeles, California. The new KRAS-mutant data, together with a growing body of EGFR-mutant data, demonstrate ATNM-400's activity across the two major mutation driver classes in NSCLC and support a distinct strategic opportunity. ATNM-400 can be developed as a potential mutation-agnostic backbone for the broader NSCLC market, alone or in combination with standard-of-care therapies, rather than as another mutation-specific drug for a narrow subset. NSCLC accounts for roughly 85% of the more than two million lung cancer cases diagnosed globally each year, a market more than twice the size of prostate cancer. It is also highly heterogeneous: no single mutation dominates, so treatments are fragmented across mutation-specific therapies such as EGFR, KRAS, BRAF, ALK and others, each marketed by different companies, each addressing only a molecular subset, and each ultimately limited by acquired resistance. ATNM-400, Actinium's first-in-class Actinium-225 (Ac-225) antibody radioconjugate, is designed to break out of that single-mutation paradigm. Rather than blocking a specific mutant protein, it delivers a high-linear-energy-transfer alpha-particle payload that induces dense, irreversible double-strand DNA breaks and tumor-cell death independent of a tumor's driver mutation or signaling pathway, the mechanistic basis of its mutation-agnostic activity. ATNM-400's target antigen, from previously published immunohistochemistry studies, is present in approximately 98% of NSCLC tumors and highly expressed in approximately 70% of those tumors. It is conserved across EGFR-, KRAS-, and other driver-defined subgroups, and further increased in tumors that have become resistant to EGFR, KRAS, and immune-checkpoint therapies. In new KRAS-mutant studies presented at SNMMI, sotorasib (active ingredient in LUMAKRAS®/Amgen) and adagrasib (active ingredient in KRAZATI®/BMS) increased ATNM-400's target up to 3.5- and 3.8-fold, respectively, and adding ATNM-400 deepened tumor-cell killing beyond either inhibitor alone. These results demonstrate the same target-expression increasing, synergy-enabling biology shown previously with the EGFR inhibitor osimertinib, which produced tumor growth inhibition of 107% when combined with ATNM-400. These combination benefits also broaden ATNM-400's commercial opportunity. The franchises it could enhance are substantial; the KRAS inhibitor class in NSCLC is projected to exceed $5 billion in peak sales, and the EGFR-mutant segment has peak sales estimates over $15 billion, led by osimertinib (active ingredient in TAGRISSO®/AZ), which generated $7.3 billion in 2025. This positions ATNM-400 to participate in these established markets by enhancing the standard of care, while also reaching the broader NSCLC population beyond any single mutation. Sandesh Seth, Actinium's Chairman and CEO, said, "Today's data further strengthen our conviction that ATNM-400 represents a fundamentally different approach to treating NSCLC solid tumors. While most targeted therapies are designed for a single mutation-defined patient population, ATNM-400 combines the mutation-independent cell-killing power of Actinium-225 with a target that is broadly expressed across tumors and becomes even more abundant as resistance emerges. The consistency of activity we have now demonstrated across both EGFR- and KRAS-driven NSCLC supports our vision for ATNM-400 as a potential mutation-agnostic backbone therapy that can be used alone or in combination across large patient populations. We believe this opportunity could extend beyond lung cancer and may position ATNM-400 as a foundational therapy across multiple solid tumor indications." Highlights from the SNMMI 2026 Poster Presentation Poster Titled: ATNM-400: A First-in-Class Actinium-225 Antibody Radioconjugate Demonstrating Durable, Mutation-Agnostic Anti-Tumor Activity in Non-Small Cell Lung Cancer Models New data demonstrated ATNM-400's potential as a mutation-agnostic antibody radioconjugate therapy for NSCLC: Across a panel of four lung cancer cell lines spanning EGFR- and KRAS-driver mutations, ATNM-400 bound and was internalized specifically by the three target-positive lines (NCI-H1975, NCI-H358 and Calu-3) but not by the target-negative line (A549), confirming that its activity is driven by target expression rather than by any particular mutation. In a KRAS G12C model (NCI-H358), PET imaging of radiolabeled ATNM-400 showed the drug concentrating in the tumor with low uptake in healthy tissue, visually confirming that it reaches its target in a living animal and delivers its alpha payload where intended while largely sparing normal organs. In a KRAS G13D model (Calu-3), a single dose of ATNM-400 drove tumor regression (124% and 135% inhibition at two dose levels), indicating marked antitumor potencywith full body-weight recovery. Deep responses from one dose with a clean tolerability profile point to a wide therapeutic window and dosing flexibility, favorable attributes for clinical translation. Treatment with both approved KRAS inhibitors (sotorasib and adagrasib) raised ATNM-400's target expression dose-dependently—up to roughly 3.5- to 3.8-fold—reaching statistical significance at every dose (p < 0.0001). The effect occurred with both agents, indicating a class-wide consequence of KRAS G12C inhibition that builds a rationale for combining ATNM-400 with these therapies. ATNM-400 plus sotorasib or adagrasib decreased cancer-cell viability beyond either inhibitor alone. The data demonstrate that ATNM-400 has development potential not only as a monotherapy but also in combination with these leading KRAS therapies and possibly the entire KRAS-mutant class. In an EGFR-mutant model (NCI-H1975), ATNM-400 monotherapy achieved 75% tumor growth inhibition versus 40% for osimertinib; combined with osimertinib it reached 107% inhibition with complete cures in 100% of mice. Osimertinib raised target expression, providing a clear rationale for the combination. About Actinium Pharmaceuticals, Inc. Actinium is a pioneer in targeted radiotherapies designed to improve outcomes for patients with cancer. The company employs a biology-driven approach to develop differentiated radiopharmaceuticals for solid tumors and hematologic malignancies. Its mission is to transform cancer treatment through innovative radioconjugates that maximize therapeutic efficacy while minimizing toxicity to healthy tissue by combining expertise in tumor biology, translational medicine, and radiochemistry. Since inception, Actinium has focused on developing innovative radiotherapies. Its pipeline reflects this strategy across three areas: (1) solid tumor therapeutics including ATNM-400 and Actimab-A with pan-tumor potential; (2) Actimab-A as a therapeutic backbone for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in collaboration with the National Cancer Institute (NCI); and (3) targeted conditioning agents including Iomab-B for bone marrow transplant and Iomab-ACT for cell and gene therapy conditioning. ATNM-400 targets a novel antigen distinct from PSMA and has demonstrated preclinical activity across metastatic castration-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC), and breast cancer. Actimab-A has shown improved survival in relapsed/refractory AML with CLAG-M and is advancing toward a Phase 2/3 trial, with additional development ongoing through a CRADA with the NCI. Actinium is also advancing preclinical solid tumor programs and holds approximately 250 patents and patent applications, including intellectual property related to cyclotron-based production of Ac-225. For more information, please visit www.actiniumpharma.com. Forward-Looking Statements This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements, including statements as related to regaining compliance with the rules of the NYSE American and submission of a compliance plan, are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on Form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time. Investors: investorrelations@actiniumpharma.com View original content to download multimedia:https://www.prnewswire.com/news-releases/actinium-presents-new-atnm-400-data-in-kras-and-egfr-mutant-models-at-snmmi-2026-supporting-a-mutation-agnostic-opportunity-in-non-small-cell-lung-cancer-302789401.html SOURCE Actinium Pharmaceuticals, Inc. Released June 3, 2026

At the moment, RevMed remains keenly focused on its mission to bring daraxonrasib to the masses and continue developing new medicines that target RAS.\n This year’s meeting of the American Society of Clinical Oncology is abuzz with talk of RAS inhibitors, largely driven by Revolution Medicines’ barnburner pancreatic cancer data drop earlier this year. But even as competitors swirl, RevMed is confident that it can maintain the leadership position it has worked so hard to obtain.“We\'re very confident in our approach, and certainly we have a head start over many other companies at this particular time,” Alan Sandler, M.D., RevMed’s chief development officer, told Fierce in Chicago.RevMed is using ASCO as a chance to shine a spotlight on the full data from the phase 3 RASolute 302 clinical trial of daraxonrasib, which enrolled 500 patients with previously treated metastatic pancreatic ductal adenocarcinoma. The results were also published in the New England Journal of Medicine today.After previously revealing that daraxonrasib doubled overall survival compared to chemotherapy, from 6.6 months to 13.2 months, RevMed has now shared a similar result for progression-free survival. The RAS inhibitor posted an average PFS of 7.3 months, compared to 3.5 months in the chemotherapy arm.Daraxonrasib’s safety profile, too, has been an open question. Now, RevMed is giving the answer. For patients given daraxonrasib, 43.6% of them had a treatment-related adverse event of grade 3 or worse, lower than the 57.5% rate in the chemotherapy arm. But the key difference is the kinds of side effects seen with daraxonrasib.While chemotherapy often led to fatigue, anemia, nausea and neutropenia, the most common side effects in the daraxonrasib group were rash, diarrhea, mouth inflammation and also nausea.“It\'s certainly a different profile from chemotherapy, and we believe more favorable for patients,” Sandler told Fierce. One patient given daraxonrasib died during the study due to lung inflammation, which the investigators deemed to be treatment related. But, Sandler said, much remains unclear about what actually happened in this case.The patient “had multiple pulmonary nodules going in” to the study, the exec explained, and was then treated for suspected pneumonia before ultimately moving to hospice care. The death was attributed to treatment out of an abundance of caution, Sandler added, but the company is “not sure what precisely happened.”This death was the only one out of 250 patients who received daraxonrasib, Sandler pointed out, with the candidate’s newly shared quality-of-life data also proving its superior safety profile in his eyes.“Not only are patients living longer, but they\'re actually feeling better while they\'re living longer,” Sandler said. Ahead of the pack RAS was long considered an undruggable target, with the first generation of inhibitors—Amgen’s Lumakras and Bristol Myers Squibb’s Krazati—showing limited efficacy because they targeted the “off” form of Ras, a group of proteins that handle important cell regulation duties.By targeting the active, “on” form of Ras, RevMed has opened the floodgates for a sea of new inhibitors to surge through. Many follow-on RAS inhibitors are likely to come from China, as the nation’s biopharma industry continues to surge thanks to its ability to quickly churn out molecules and push them into the clinic. But some of RevMed’s rivals come from inside America’s borders, and they are hardly upstart biotechs.Gilead Sciences is one compatriot that has gotten into the RAS game, albeit still at an early stage. The pharma’s Chief Medical Officer Dietmar Berger, M.D., Ph.D., told Fierce at ASCO that he believes progress in the red-hot RAS world is still possible. “There is an opportunity to innovate even further,” he said. In addition to compounds like daraxonrasib that work on a variety of RAS mutations, there are also RAS degraders, he explained, and Gilead has an eye on them all. Of course, RevMed is hardly slowing down itself when it comes to advancing the potential of RAS inhibition. The biotech, headquartered in Redwood City just down the road from Gilead’s Foster City HQ, endeavors to bring daraxonrasib into first-line pancreatic cancer and other RAS-dependent cancers while also forging ahead with next-gen molecules that combat the resistance that cancer can develop to the star molecule.The key candidate here is the preclinical RM-055. RAS-dependent cancers can overcome inhibition by pumping out more and more RAS. RM-055 is designed to flip RAS from its active state to an inactive one, to counteract this proliferation. RevMed is also continuing to explore the intricacies of RAS biology, Sandler said.“Our belief is that the RAS pathway, once mutated and activated in a cancer, always remains important,” he told Fierce. “Continuing to attack that is going to be key.”It goes without saying that no matter what RevMed does next, it will have a large audience watching closely. Speculation has swirled about the potential for a Big Pharma to scoop up the RAS specialist, while others think RevMed has become too valuable for many companies to afford.At the moment, though, RevMed remains keenly focused on its mission to bring daraxonrasib to the masses and continue developing new medicines that target RAS, which is overexpressed on more than 90% of pancreatic cancers, 60% of colorectal cancers and 30% of non-small cell lung cancers, Sandler said.RevMed’s pipeline also includes another pancreatic cancer candidate called zoldonrasib, as well as the earlier solid tumor asset elironrasib. The biotech is also open to partnerships, like its ongoing pact with Summit Therapeutics, and expects many other potential partners to come knocking if daraxonrasib secures FDA approval.“We\'re working full steam ahead on building our global company and building it to be able to take care of cancer patients with RAS-driven cancers,” Sandler said. “About 30% of all cancers are RAS-driven, so that\'s a huge potential impact.”