Aldesleukin

LARKSPUR, Calif.--(BUSINESS WIRE)--Aulos™ Bioscience, an immuno-oncology company working to revolutionize cancer care through development of its lead immune-activating antibody therapeutic, today presented positive results from its Phase 1/2 dose escalation and cohort expansion study of its investigational candidate AU-007. The data were shared in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting in Chicago, Illinois. The interim Phase 2 data demonstrate clear evidence of durable partial and complete tumor response in multiple cancer types, including patients with melanoma whose tumors had progressed through prior checkpoint inhibitors and who received a combination of AU-007 and low-dose, subcutaneous aldesleukin. Durable tumor shrinkages were also observed in patients with checkpoint inhibitor-resistant or progressed renal cell carcinoma (RCC) who received the same AU-007 and aldesleukin regimen. Additionally, AU-007 and low-dose, subcutaneous aldesleukin continues to demonstrate a unique pharmacodynamic (PD) profile in the interleukin-2 (IL-2) class, with regulatory T cells (Tregs) decreasing and CD8 effector T cells expanding at all AU-007 dose levels. “We are very pleased with the clinical activity observed with AU-007 and low-dose, subcutaneous aldesleukin without a checkpoint inhibitor, as it accentuates our confidence in AU-007 as a potential best-in-class therapeutic for multiple cancers,” said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer. “Deep and durable tumor shrinkages, including complete responses, are occurring in patients who were refractory to treatment and had achieved no responses from highly potent prior immuno-oncology regimens. Importantly, the results reinforce the previously reported observation that the CD8 effector T cell expansion and Treg reduction correlates with clinical efficacy. This key driver of Treg reduction coupled with CD8 effector T cell expansion and enhancement of the CD8/Treg ratio differentiates AU-007 from other IL-2 therapeutic programs. Today’s data support further evaluation of AU-007 and low-dose, subcutaneous aldesleukin as a second-line treatment for melanoma, where limited treatment options exist. Our new Phase 2 cohort augmenting this regimen with anti-PD-1 nivolumab is now enrolling patients and we look forward to presenting preliminary data later this year.” Key findings from interim results of the Phase 1/2 dose escalation and cohort expansion study of AU-007, with data available on 95 patients as of the data cutoff date of March 20, 2025, are as follows: Continued tolerable and manageable safety profile was observed with AU-007 as a monotherapy and in combination with low-dose, subcutaneous aldesleukin at all doses evaluated in Phase 1 dose escalation. No dose-limiting toxicity occurred throughout Phase 1 dose escalation. Most drug-related adverse events were mild and transient Grade 1 or 2 events. The most common treatment-related adverse events in patients who received AU-007 and low-dose, subcutaneous aldesleukin were Grade 1 or 2 fatigue (21%), pyrexia (21%), chills (19%) and infusion-related reaction (15%). The incidence of Grade 3 or 4 treatment-related adverse events in patients who received AU-007 and low-dose, subcutaneous aldesleukin was cytokine release syndrome (1%), lymphopenia (8%) and anemia (3%). All events were transient and resolved, and there were no Grade 5 treatment-related adverse events. Durable objective responses were observed in patients with multiple tumor types enrolled in the Phase 1 dose escalation and Phase 2 cohorts. One patient with metastatic bladder cancer that progressed on an anti-PD-L1 treatment was treated with AU-007 every two weeks (Q2W) and one loading dose of low-dose, subcutaneous aldesleukin, has an ongoing metabolic complete response and continues on treatment for two years. One patient with metastatic nasopharyngeal head and neck cancer that progressed on five prior systemic therapies received AU-007 and low-dose, subcutaneous aldesleukin Q2W. This patient experienced an unconfirmed complete response after 20 months and continues on treatment. Three patients with melanoma refractory to either prior anti-CTLA-4 and anti-PD-1 or anti-PD-1 and anti-LAG-3 therapy were treated with AU-007 Q2W and one loading dose of low-dose, subcutaneous aldesleukin, and experienced deep and durable tumor shrinkages of 100% (complete response in all target lesions, continues on study for 13+ months), 58% (continues on study for 10+ months) and 48% (on study for 13 months). One patient in dose escalation with acral melanoma that progressed rapidly on prior anti-PD-1 therapy received AU-007 and one loading dose of low-dose, subcutaneous aldesleukin. This patient remained on AU-007 therapy for 11 months with disease control. The regimen of AU-007 and low-dose, subcutaneous aldesleukin exhibits distinct pharmacodynamic effects in the class and continues to drive durable decreases in Tregs, increases in CD8 T cells, and corresponding increases in CD8/Treg ratios. A decrease in Tregs appears to be a critical determinant of observed efficacy, with Tregs decreasing in the periphery in the presence of AU-007 at all dose levels. This finding supports AU-007’s overall mechanism of action to control and redirect endogenously produced IL-2 and exogenously administered IL-2 to reduce the Treg population and increase circulating CD8 effector T cell populations. Treg cells are highly immunosuppressive cells that can blunt the immune response to tumors and reduce the durability of responses and progression-free survival. The Phase 2 expansion cohorts evaluating AU-007 and a single loading dose of low-dose, subcutaneous aldesleukin continue to enroll patients with advanced cutaneous melanoma who have failed prior checkpoint inhibitor therapy as well as patients with PD-L1+ non-small cell lung cancer (NSCLC) who have failed prior checkpoint inhibitor therapy. An additional Phase 2 cohort is evaluating AU-007 and low-dose, subcutaneous aldesleukin combined with avelumab (checkpoint inhibitor with ADCC effector function; anti-PD-L1) in PD-L1+ NSCLC in patients who have failed prior checkpoint inhibitor therapy. As announced earlier this month, a new Phase 2 cohort evaluating AU-007 and a single subcutaneous loading dose of low-dose aldesleukin combined with nivolumab (checkpoint inhibitor; anti-PD-1) as a second-line treatment for cutaneous melanoma is enrolling patients who have not received a prior BRAF/MEK inhibitor. Aulos anticipates presenting preliminary clinical data from these two Phase 2 expansion cohorts in the second half of 2025. The poster, “AU-007, a human monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, plus low-dose aldesleukin, in advanced solid tumors: Phase 2 update,” (Abstract CT178) is accessible to meeting registrants as an electronic poster on the AACR 2025 virtual meeting platform. It is also available on the Aulos Bioscience website in the Abstracts and Publications section. To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit www.solidtumorstudy.com. For patients and health professionals in Australia, please visit www.solidtumourstudy.com. About AU-007 AU-007 is a human IgG1 monoclonal antibody designed by leveraging artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 redirects IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy. About Aulos Aulos Bioscience is an immuno-oncology company working to revolutionize cancer patient care through immune-activating antibody therapeutics that direct patients’ immune systems toward killing tumor cells. Matching world-class machine learning from co-founder Biolojic Design with an in-depth understanding of the immune system, Aulos’ initial clinical candidate, AU-007, is a human antibody designed by leveraging artificial intelligence that harnesses the power of IL-2 to induce tumor killing while limiting the immunosuppression and toxicities typically associated with this validated pathway. The company was founded by Biolojic Design and Apple Tree Partners (ATP) and is led by pioneers in the fields of artificial intelligence, antibody development and cancer immunotherapies. For more information, visit www.aulosbio.com, X (@AulosBioscience) and LinkedIn.

Ten (10) patients have achieved an objective response (5 confirmed) when treated with MDNA11 alone or in combination with KEYTRUDA® (pembrolizumab) – all responders had advanced and/or metastatic cancers with resistance to immune checkpoint inhibitors (ICI) or with historically low responses to ICI Combination of MDNA11 with KEYTRUDA in the dose escalation arm achieved an objective response rate (ORR) of 36% (5 of 14) in all tumor types enrolling in the Phase 2 expansion cohorts and an ORR of 31% (4 of 13) in cancers planned for the Phase 2 combination expansion cohort Patients from MDNA11 monotherapy dose expansion and dose escalation arms treated at ≥ 60 µg/kg achieved an ORR of 29.4% (5 of 17) in all tumor types enrolling in the Phase 2 expansion cohorts and an ORR of 40% (4 of 10) in cancers enrolling in the Phase 2 monotherapy expansion cohort Highest ORR of 50% achieved amongst MSI-H patients receiving MDNA11 monotherapy (2 of 4) and endometrial cancer patients receiving a combination of MDNA11 and KEYTRUDA (2 of 4) Monotherapy arm continues to demonstrate encouraging durability with a melanoma patient and a pancreatic cancer patient remaining tumor-free and off-treatment after entering the study 2 and 3 years ago, respectively Enrollment in the Phase 2 combination dose expansion arm is underway with the MDNA11 combination Recommended Dose for Expansion (cRDE) established at 90 µg/kg (every 2 weeks) together with KEYTRUDA (400 mg every 6 weeks) Tumor types being evaluated in the Phase 2 expansion cohorts include MSI-H/dMMR, TMB-H, virally-derived cancers (monotherapy), gynecological cancers (combination) and cutaneous melanoma with (combination) or without primary resistance to ICI (monotherapy and combination arms) Additional monotherapy and combination data from the ABILITY-1 study expected at future medical conferences throughout this calendar year TORONTO and HOUSTON, April 28, 2025 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA, OTCQX: MDNAF), a clinical-stage immunotherapy company focused on the development of Superkines targeting cancer and autoimmune diseases, today presents updated clinical data from the ongoing Phase 1/2 ABILITY-1 study evaluating MDNA11 in patients with advanced solid tumors at the 2025 Annual Meeting of the American Association for Cancer Research (AACR) in Chicago, Illinois. MDNA11, a long-acting ‘beta-enhanced not-alpha’ interleukin-2 (IL-2) super-agonist, is being evaluated as a monotherapy or in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab). “We are encouraged by the anti-tumor activity and safety of MDNA11 in both the monotherapy and combination setting, including the 3 recent responders, particularly in patients who have shown resistance to checkpoint inhibitors or with tumor types with historically low responses to immunotherapies and addressing a vastly underserved cancer population,” commented Fahar Merchant, PhD, President and CEO of Medicenna. “Today’s efficacy and immunodynamic data have provided the foundation to commence the dose expansion portion for MDNA11 in combination with KEYTRUDA. In the monotherapy setting, we continue to see deep and durable single agent activity of MDNA11 with two patients remaining in complete remission and off therapy. Together, these data reinforce the best-in-class potential for MDNA11 as a potent and safe immunotherapy that is poised to transform the existing treatment paradigm for patients with difficult-to-treat tumors. We look forward to sharing additional clinical data from the ABILITY-1 study at future medical conferences this year.” Key findings from the on-going ABILITY-1 study (data cut-off as of April 15, 2025) include: Safety Profile MDNA11 continues to demonstrate an acceptable safety profile both as a single agent and in combination with KEYTRUDA. Over 90% of treatment-related adverse events (TRAEs) were Grade 1-2 and transient, with no dose limiting toxicities (DLTs) observed with MDNA11 at doses up to 120 µg/kg (Q2W) in monotherapy and in combination with KEYTRUDA (400 mg, Q6W). Immunodynamics Robust expansion of immune effector cells in monotherapy and combination with KEYTRUDA with notable increases in effector (DNAM), ‘stemness-like’ (TCF-1) and memory CD8+ T cells, which are critical for sustained anti-tumor responses.Robust, dose-dependent lymphocyte expansion in combination with KEYTRUDA, sustained with repeat MDNA11 dosing, and plateauing at the 90 µg/kg MDNA11 dose level. Clinical Activity of MDNA11 in Combination with KEYTRUDA during Dose Escalation Enrollment in the combination dose expansion portion of the ABILITY-1 study is underway having established the MDNA11 combination Recommended Dose for Expansion (cRDE) at 90 µg/kg administered every 2 weeks together with KEYTRUDA administered at 400 mg every 6 weeks. Encouraging anti-tumor activity continues to be observed with MDNA11 in combination with KEYTRUDA in patients enrolled in the dose escalation portion of the study: 5 objective responses (1 CR and 4 PRs) among heavily pre-treated patients, including two previously reported objective responses in historically low immunotherapy responders: 70-year-old male with anal squamous cell carcinoma (SCC) who previously progressed on two prior lines of chemotherapy achieved a CR on the first study evaluable imaging scan (week 8); patient continues on combination treatment following a confirmed CR.52-year-old female with TMB-H/MSS colorectal cancer who previously progressed on two prior lines of chemotherapy achieved a confirmed PR. While off-study for 4 months, the patient continues to show deepening of the tumor response in the absence of any treatment. Objective response rate (ORR) of 31% (4 of 13) in patients with cancers planned for the Phase 2 combination expansion cohort, including cutaneous melanoma, MSI-H/dMMR, and TMB-H tumors, and an ORR of 36% (5 of 14) when including the virally-derived cancers.Stable disease (SD) in 3 patients for a disease control rate (DCR = CR+PR+SD) of 57% (8/14). Monotherapy Tumor Response in Immune Checkpoint Inhibitor-Resistant Patients MDNA11 continues to demonstrate encouraging deep and durable single-agent anti-tumor activity among patients who progressed on prior immune checkpoint inhibitor (ICI) therapy: ORR of 40% in the monotherapy dose escalation (treated at ≥ 60 μg/kg) and expansion arm (1 confirmed CR, 1 confirmed PR and 2 unconfirmed PRs) among 10 patients with tumor types currently enrolling in the Phase 2 monotherapy expansion cohort. All patients had previously failed ICI therapy and had advanced and/or metastatic cutaneous melanoma with secondary resistance to ICI or MSI-H/dMMR tumors. Note that the non-melanoma skin cancer cohort is not recruiting as it was replaced with a new cohort of virally-derived cancers subsequent to a protocol amendment. The ORR is 29.4% from a total of 17 patients when including patients with cancers planned for Phase 2 expansion cohort and patients with primary ICI resistant melanoma who received at least 60 µg/kg of MDNA11 (Q2W).Overall, objective responses in ICI-resistant patients include 1 CR and 4 PRs 2 PRs among 4 MSI-H patients (ORR of 50%) with both responders having metastatic pancreatic ductal adenocarcinoma (PDAC).1 CR and 1 PR among 6 patients with ICI secondary resistant melanoma (ORR of 33.3%).1 PR among patients with ICI primary resistant melanoma. Complete resolution of all target and non-target lesions in two patients with on-going remission following end-of-treatment: Cutaneous melanoma patient achieved a durable response exceeding 12 months during the study with complete resolution of target and non-target metastatic lesions, and continues to remain off anti-cancer therapy for more than 6 weeks.Pancreatic cancer patient (MSI-H) achieved a durable response for 20 months during the study with complete resolution of target and non-target metastatic lesions in the liver including a new lesion treated with MDNA11 following a single cycle of radiation, and continues to remain off anti-cancer therapy for more than 12 months. SD in 6 patients for a disease control rate (DCR = CR+PR+SD) of 65% including 2 with duration > 6 months, yielding a clinical benefit rate of 41% (7/17). A copy of the poster and related slide deck has been posted on the “Scientific Presentations” page of Medicenna’s website. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About MDNA11 MDNA11 is an intravenously administered, long-acting, ‘beta-enhanced not-alpha’ IL-2 Superkine specifically engineered to overcome the shortcomings of aldesleukin and other next generation IL-2 variants by preferentially activating immune effector cells (CD8+ T and NK cells) responsible for killing cancer cells, with minimal or no stimulation of immunosuppressive Tregs. These unique proprietary features of the IL-2 Superkine have been achieved by incorporating seven specific mutations and genetically fusing it to a recombinant human albumin scaffold to improve the pharmacokinetic (PK) profile and pharmacological activity of MDNA11 due to albumin’s natural propensity to accumulate in highly vascularized sites, in particular tumor and tumor draining lymph nodes. MDNA11 is currently being evaluated in the Phase 1/2 ABILITY-1 study as both monotherapy and in combination with KEYTRUDA®. About the ABILITY-1 Study The ABILITY-1 study (NCT05086692) is a global, multi-center, open-label study that assesses the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of MDNA11 as monotherapy or in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab). In the combination dose escalation portion of the Phase 2 study, patients have been enrolled and administered ascending doses of MDNA11 intravenously in combination with KEYTRUDA. This portion of the study includes patients with a wide range of solid tumors with the potential for susceptibility to immune modulating therapeutics. The combination Recommended Dose for Expansion (cRDE) has been established and the study has commenced combination dose expansion. About Medicenna Therapeutics Medicenna is a clinical-stage immunotherapy company focused on developing novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines and first-in-class Empowered Superkines. Medicenna’s long-acting IL-2 Superkine, MDNA11, is a next-generation IL-2 with superior affinity toward CD122 (IL-2 receptor beta) and no CD25 (IL-2 receptor alpha) binding, thereby preferentially stimulating cancer-killing effector T cells and NK cells. MDNA11 is being evaluated in the Phase 1/2 ABILITY-1 Study (NCT05086692) as a monotherapy and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab). Medicenna’s IL-4 Empowered Superkine, bizaxofusp (formerly MDNA55), has been studied in 5 clinical trials enrolling over 130 patients, including a Phase 2b trial for recurrent GBM, the most common and uniformly fatal form of brain cancer. Bizaxofusp has obtained FastTrack and Orphan Drug status from the FDA and FDA/EMA, respectively. Medicenna’s early-stage high-affinity IL-2β biased IL-2/IL-15 Super-antagonists, from its MDNA209 platform, are being evaluated as potential therapies for autoimmune and graft-versus host diseases. Medicenna’s early-stage BiSKITs™ (Bifunctional SuperKine ImmunoTherapies) and the T-MASK™ (Targeted Metalloprotease Activated SuperKine) programs are designed to enhance the ability of Superkines to treat immunologically “cold” tumors. For more information, please visit www.medicenna.com, and follow us on Twitter and LinkedIn. Forward-Looking Statements This news release may contain forward-looking statements within the meaning of applicable securities laws. Forward-looking statements include, but are not limited to, express or implied statements regarding the future operations of the Company, estimates, plans, strategic ambitions, partnership activities and opportunities, objectives, expectations, opinions, forecasts, projections, guidance, outlook or other statements that are not historical facts, such as statements on the therapeutic treatment potential and safety profile of MDNA11 (both as monotherapy and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® [pembrolizumab]) and the timing and/or release of any additional clinical updates. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage pre-clinical or clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. 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Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date hereof and except as required by law, we do not intend and do not assume any obligation to update or revise publicly any of the included forward-looking statements. This news release contains hyperlinks to information that is not deemed to be incorporated by reference in this new release. Investor and Company Contact: Christina CameronInvestor Relationsir@medicenna.com(647) 953-0673