Last update 11 Dec 2024

Aldesleukin

Last update 11 Dec 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Interleukins

Synonyms

125-L-Serine-2-133-interleukin 2, IL-2 (Chiron), Interleukin-2 (Chiron)

+ [12]

Target

IL-2R

Mechanism

IL-2R agonists(Interleukin-2 receptor agonists), Immunostimulants

Therapeutic Areas

NeoplasmsUrogenital DiseasesSkin and Musculoskeletal Diseases+ [5]

Active Indication

Renal Cell CarcinomaNeuroblastoma recurrentMalignant melanoma, metastatic+ [13]

Inactive Indication

Acute Basophilic LeukemiaAcute Eosinophilic LeukemiaAcute Erythroblastic Leukemia+ [85]

Originator Organization

Chiron Corp.

Active Organization

Clinigen

National Cancer InstituteClinigen Healthcare Ltd.

+ [7]

Inactive Organization

Barbara Ann Karmanos Cancer Institute

National Institute on AgingNational Institutes of Health Clinical Center

Drug Highest PhaseApproved

First Approval Date

US (05 May 1992),

Renal Cell Carcinoma

RegulationOrphan Drug (KR), Orphan Drug (US)

Gene Sequence

Sequence Code 720

Source: *****

421

Clinical Trials associated with Aldesleukin

NCT06690281 / Not yet recruitingPhase 2IIT

A Phase II Study of Adjuvant Immunotherapy Targeting KRAS G12D, KRAS G12V, or TP53 R175H for Participants With Advanced Gastrointestinal Malignancies

Background:
Gastrointestinal (GI) cancer affects the organs (such as the stomach, large and small intestine, pancreas, colon, liver, and biliary system) of the digestive tract. In some participants who have had surgery for GI cancer, blood tests show that the cancer has spread despite being unable to be identified by scans. Certain gene mutations (changes) in GI cancer (such as KRAS or TP53) can be targeted by T cells, a type of immune cell, in individuals with specific HLA types (genes that help proteins in the body know what is self and non-self). Researchers want to see if they can stop GI cancer from returning or spreading in people with these gene mutations and specific HLA types.
Objective:
To test therapy with modified T-cells to prevent or delay the return of GI cancer after standard treatment. T-cells play a role in the body s immune system.
Eligibility:
People aged 18 to 72 years with GI cancer that was treated with standard therapy and is not seen on imaging scans. They must have specific gene mutations and HLA types. They also must have certain clinical or blood tests showing the cancer is spreading (elevating CA19-9 or detectable ctDNA).
Design:
Participants will be divided into 2 groups. Participants nor the study team can choose what Group to participate in; this is done by randomization , like flipping a coin. Participants will have a 1-to-1 chance of being in Group 1 or Group 2.
Group 1 will receive T-cell therapy. Their own T-cells will be collected. In a lab, the cells will be combined with a virus that carries a protein to target cancer cells.
Group 1 participants will stay in the hospital for 3 weeks or more. They will have chemotherapy, and their modified T-cells will be infused through a tube attached to a needle inserted into a vein.
Group 1 participants will visit the clinic every 3 months for 1 year and then every 6 months for 5 years. Then they will have follow-up visits for another 10 years under a different protocol.
Group 2 participants will not receive treatment with T-cells. They will visit the clinic every 3 months for 1 year and then every 6 months for 5 years.

Start Date01 Jan 2025

Sponsor / Collaborator

National Cancer Institute

NCT06626256 / Not yet recruitingPhase 1IIT

A Phase 1 Safety and Efficacy Study of STIL101 for Injection in Locally Advanced, Unresectable, or Metastatic Pancreatic Ductal Adenocarcinoma, Colorectal Cancer, Renal Cell Carcinoma, Cervical Cancer, and Melanoma

This phase I trial tests the safety and side effects of STIL101 for injection and how well it works in treating patients with pancreatic cancer, colorectal cancer (CRC), renal cell cancer (RCC), cervical cancer (CC) and melanoma that has spread to nearby tissue or lymph nodes (locally advanced) or to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). STIL101 for injection, an autologous (made from the patients own cells) cellular therapy, is made up of specialized white blood cells called lymphocytes or "T cells" collected from a piece of the patients tumor tissue. The T cells collected from the tumor are then grown in a laboratory to create STIL101 for injection. STIL101 for injection is then given to the patient where it may attack the tumor. Giving chemotherapy, such as cyclophosphamide and fludarabine, helps prepare the body to receive STIL101 for injection in a way that allows the T cells the best opportunity to attack the tumor. Aldesleukin is a form of interleukin-2, a cytokine made by leukocytes. Aldesleukin increases the activity and growth of white blood cells called T lymphocytes and B lymphocytes. Giving STIL101 for injection may be safe, tolerable and/or effective in treating patients with locally advanced, metastatic or unresectable pancreatic cancer, CRC, RCC, CC and melanoma.

Start Date30 Dec 2024

Sponsor / Collaborator

City of Hope National Medical Center

[+1]

NCT05639972 / Not yet recruitingPhase 1/2IIT

A Feasibility Study of E7 TCR-T Cell Induction Therapy for Locoregionally Advanced HPV-Associated Cancers

The goal of this study is to determine the feasibility of administration of a single dose of E7 TCR-T cells as induction therapy prior to definitive treatment (chemoradiation or surgery) of locoregionally advanced HPV-associated cancers. The intent of E7 TCR-T cell treatment is to shrink or eliminate tumors and thereby facilitate definitive therapy and increase overall survival.
This study seeks to determine 1) if E7 TCR-T cells can be administered without undue delay in definitive treatment, 2) the tumor response rate to E7 TCR-T cell treatment, and 3) the disease-free survival rate at 2 and 5 years.
Participants will undergo an apheresis procedure to obtain T cells that will be genetically engineered to generate E7 TCR-T cells. They will receive a conditioning regimen, a single infusion of their own E7 TCR-T cells, and adjuvant aldesleukin. Participants will follow up to assess safety and determine tumor response and will return to their primary oncology team for definitive therapy.

Start Date12 Oct 2024

Sponsor / Collaborator

Rutgers State University of New Jersey

100 Clinical Results associated with Aldesleukin

100 Translational Medicine associated with Aldesleukin

100 Patents (Medical) associated with Aldesleukin

2,992

Literatures (Medical) associated with Aldesleukin

31 Dec 2024·mAbs

Discovery and development of ANV419, an IL-2/anti-IL-2 antibody fusion protein with potent CD8+ T and natural killer cell-stimulating capacity for cancer immunotherapy

Article

Author: Regnier, Catherine ; Rondeau, Jean-Michel ; Popp, Simone ; Katopodis, Andreas ; Egli, Nicole ; Huber, Christoph ; Richter, Kirsten ; Murer, Patrizia ; Petersen, Laetitia ; Brannetti, Barbara

Novel engineered IL-2 agonists strive to increase the therapeutic window of aldesleukin (human IL-2) by increasing selectivity toward effector over regulatory T cells and reducing dose-limiting toxicities. Here we describe ANV419, an IL-2/anti-IL2 antibody fusion protein designed for selective IL-2 receptor βγ (IL-2 Rβγ) activation by sterically hindering IL-2 from binding to IL-2 Rα. The fusion protein has an IL-2 connected to the light chain complementarity-determining region (CDR) domain of a humanized antibody that binds to IL-2 at the same epitope as IL-2 Rα. Optimization of the selectivity and pharmacological properties led to the selection of ANV419. ANV419 preferentially expands CD8⁺ T cells and natural killer (NK) cells over T_regs and can be safely administered at doses that elicit strong pharmacodynamic effects and efficacy in mouse tumor models. Its anti-tumor efficacy was enhanced when combined with programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors. ANV419 also enhances the NK cell killing capacity and increases tumor growth inhibition when used alongside trastuzumab in a Her-2⁺ xenograft mouse model. In cynomolgus monkeys, the estimated half-life of ANV419 is 24 h, and doses that induced sustained expansion of effector cells were well tolerated without the severe toxicities typically observed with high-dose IL-2. These data support the clinical development of ANV419 in solid tumors and hematological malignancies as monotherapy and in combination with checkpoint inhibitors or agents that induce antibody-dependent cellular cytotoxicity. ANV419 is currently in Phase 1/2 clinical development and may provide cancer patients with a wider therapeutic window than aldesleukin.

01 Nov 2024·Rheumatology (Oxford, England)

Where are we now in biologic drugs for myositis?

Review

Author: Isenberg, David A ; Neves, Ana ; Viveiros, Luísa ; Venturelli, Veronica

Abstract:

Idiopathic inflammatory myopathies (IIMs) are a rare and heterogeneous group of chronic autoimmune disorders. Up to 40% of IIM patients have long-term sequelae and significant functional disability. Its management can be challenging and new therapies are badly needed. The small number of cases with diverse presentations and different diagnostic criteria significantly affect clinical trial results. Only IVIG has been internationally approved for IIM patients. Most clinical trials of new biologic therapies have failed to meet their primary endpoints in IIM, with only one biologic drug recommended for refractory IIM treatment (rituximab), although not approved. We review several new emerging biologic drugs, including B cell depletion therapies, abatacept, Janus kinase inhibitors, and aldesleukin. Encouragingly, some phase II randomized controlled trials have evaluated the efficacy and safety of new biologics in IIM, demonstrating an improvement in clinical and laboratory measures.

01 Nov 2024·IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY

Immunosuppressive effects of triptolide via interleukin-2/receptor signaling

Article

Author: Ding, Yanxia ; Wang, Juan ; Lv, Jiagang ; Darshika Kodithuwakku, Nandani ; Xiong, Ying ; Yin, Yi ; Chen, Jiao

BACKGROUND:

Triptolide (TP) has been confirmed to possess many beneficial functions including anti-inflammation and immunosuppression.

OBJECTIVE:

The present study aimed to explore the potential involvement of IL-2/IL-2R pathway in the immunosuppressive activities of TP.

METHODS:

Cultured CTLL-2 cells were utilized to evaluate the potential benefits of TP. Then cell viability was determined by CCK-8 assay, IFN-γ level by ELISA assay, Annexin V-FITC/PI double-staining and CD25 expression by flow cytometry, and protein expression by western blotting. Additionally, rhIL-2-driven lymphocytes following ConA activation were investigated. The interactions of TP with IL-2 and IL-2Rα were investigated by binding assays and molecular dynamics simulations.

RESULTS:

TP treatment attenuated IFN-γ level and cell viability in both rhIL-2-induced CTLL-2 cells and rhIL-2-driven splenic lymphocytes. TP treatment increased cellular apoptosis/necrosis and cleaved PARP-1 level, while suppressed c-Myc level in rhIL-2-induced CTLL-2 cells. Additionally, TP treatment reduced CD25 expression on CTLL-2 cell surface. Notably, the phosphorylation protein levels in IL-2R signaling pathways were inhibited by TP exposure prior to rhIL-2 stimulation. SPR and BLI assays verified TP that directly bound to rhIL-2 and rmIL-2Rα, respectively. Molecular simulations suggested that TP bound at the interface of IL-2 and IL-2Rα near the hydrophobic patch composed of F62, L92 on IL-2 and L23, I46, V139 on IL-2Rα, resulting in decreased binding free energy between IL-2 and IL-2Rα.

CONCLUSIONS:

These findings collectively emphasized that TP interfered IL-2/IL-2Rα interactions, down-regulated IL-2Rα expression, and inhibited IL-2R signaling pathways activation, thereby leading to the immune cells being desensitized to rhIL-2 and exhibiting immunosuppressive properties.

News (Medical) associated with Aldesleukin

05 Dec 2024

·www.globenewswire.com

Medicenna Provides Clinical Update and Announces First Complete Responder in MDNA11 and KEYTRUDA® (pembrolizumab) Combination Dose Escalation Arm of the ABILITY-1 Study

70-year-old patient with advanced chemo-refractory anal cancer achieves complete response (CR) in 8 weeks when treated with MDNA11 in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) Complete regression of all tumors in two CPI-resistant patients in monotherapy arms continue to show durability with a patient with melanoma remaining tumor free at week 63 while a patient with pancreatic cancer remains off all anti-cancer therapy for 11 months after completing the study A patient with advanced MSS colorectal cancer with a previously announced partial response (PR) continues treatment in the combination escalation arm as of week 32 with a confirmed PR Both objective responses (1 CR and 1PR) among evaluable patients in the combination dose escalation arm (N=9) are in tumor types with high unmet need and where checkpoint inhibitors (CPI) have not been approved The ABILITY-1 study is showing promising disease control rates (DCR = CR+PR+SD) of 55% (1 CR, 4 PRs, and 6 SDs) and 78% (1 CR, 1 PR and 5 SDs) in the monotherapy and combination arms, respectfully Additional monotherapy and combination clinical data from the ABILITY-1 study will be presented at medical conferences in Q1 and Q2 of 2025 TORONTO and HOUSTON, Dec. 05, 2024 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA, OTCQX: MDNAF), a clinical-stage immunotherapy company focused on the development of Superkines, announced that updated clinical data from the ongoing Phase 1/2 ABILITY-1 study were presented today at the 2024 Immunotherapy Bridge held in Naples, Italy. The oral presentation by Dr Arash Yavari, MB BS, DPhil, included new data highlighting the first complete response (CR) in the combination dose escalation phase of the study in a 70-year-old patient with advanced anal squamous cell carcinoma (anal SCC), in addition to follow up safety and efficacy results from the monotherapy and combination arms of the ABILITY-1 study. The anal SCC patient previously progressed on two prior lines of treatment comprising of chemotherapy combination and chemo-radiation treatments. The patient achieved a 100% reduction of all measurable target and non-target lesions by Week 8, highlighting MDNA11’s potential to enhance checkpoint inhibitor efficacy in advanced solid tumor types traditionally considered less sensitive to immunotherapy. “These remarkable results from our monotherapy and early data from the combination dose escalation highlights the transformative potential of MDNA11 as a combination therapy with checkpoint inhibitors like KEYTRUDA®, while demonstrating an acceptable safety profile as dose escalation continues,” said Fahar Merchant, PhD, President and CEO of Medicenna. “Achieving a complete response in a patient with anal squamous cell carcinoma, a cancer with historically low immunotherapy response rates, demonstrates MDNA11’s ability to reinvigorate the immune system and tackle difficult-to-treat tumors. We look forward to sharing additional clinical data at medical conferences in Q1 and Q2 of 2025 as we advance MDNA11 as a potent and safe immunotherapy to dramatically improve current immunotherapies and deliver life-changing outcomes for patients.” Key findings from the on-going ABILITY-1 study (data cut-off as of November 18th, 2024) include: Safety Profile MDNA11 has a favorable safety profile both as a monotherapy and in combination with KEYTRUDA®. Over 90% of treatment-related adverse events (TRAEs) were Grade 1-2 and transient, with no DLTs or new safety signals observed in combination dose escalation cohorts. MDNA11 at doses of 120 µg /kg (Q3W monotherapy; Q2W and Q3W in combination with Keytruda (400 mg Q6W) are currently being evaluated. Immunodynamics MDNA11 preferentially expands immune effector cells, including activated (CD25+) and “stemness-like” (TCF-1+) 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. 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 ICI therapy: An objective response rate (ORR) of 30% in the monotherapy dose expansion arm with 3 PRs among 10 patients who had all previously failed ICI therapy and had advanced and/or metastatic melanoma, non-melanoma skin cancer or MSI-H/dMMR tumors. The ORR is 25% from a total of 20 patients when including 10 phase 2 eligible patients from the MDNA11 monotherapy dose escalation arm who received at least 60 µg/kg MDNA11 and were ICI-resistant.Overall, objective responses in ICI-resistant patients include 1 CR and 4 PRs 2 PRs among 3 MSI-H patients (ORR of 66.7%) with both responders having metastatic pancreatic ductal adenocarcinoma (PDAC).1 CR and 2 PRs among 11 patients with cutaneous melanoma (ORR of 27.3%). Complete resolution of all target and non-target lesions in two patients: 1 confirmed CR in a melanoma patient continues on treatment as of week 63.Pancreatic cancer patient (MSI-H) achieved 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, achieved durable response for 20 months during the study and continues to remain off anti-cancer therapy for 11 months. SD in 6 patients for a disease control rate (DCR = CR+PR+SD) of 55% including 3 with duration > 6 months, yielding a clinical benefit rate of 40% (8/20). MDNA11 Combination with KEYTRUDA® Tumor Response The objective of the combination dose escalation/evaluation portion of the ABILITY-1 study is to assess the safety, pharmacokinetics and immunodynamics of MDNA11 at various doses and dosing regimens when combined with KEYTRUDA® (400mg, Q6W), and to determine the recommended dose and schedule for the combination dose expansion portion of the study. Encouraging preliminary signs of anti-tumor activity have been observed with MDNA11 in combination with KEYTRUDA® to date in dose escalation cohorts 1 (60 µg/kg Q2W MDNA11) and 2 (90 µg/kg Q2W MDNA11). Among 9 heavily pre-treated, efficacy-evaluable patients, tumor control was observed in 7 patients for a DCR of 78% including a CR in an anal squamous cell carcinoma patient and PR in a microsatellite-stable (MSS) colorectal cancer patient. CR in a 70-year-old male with anal squamous cell carcinoma Patient progressed on 2 prior lines of chemotherapy (1L capecitabine/mitomycin plus radiation therapy; 2L carboplatin/paclitaxel)CR achieved on first study evaluable imaging scan at Week 8; patient continues on combination treatment Confirmed PR in 52-year-old female with MSS colorectal cancer Patient progressed on 2 prior lines of chemotherapy (1L folinate/fluorouracil/oxaliplatin; 2L capecitabine)Continues on combination treatment as of week 32 A copy of the presentation has been posted on the “Scientific Presentations” page of Medicenna’s website. 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 KEYTRUDA®. In the combination dose escalation portion of the Phase 2 study, approximately 20 patients are expected to be 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. Upon identification of an appropriate dose regimen for combination, the study will proceed to 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 KEYTRUDA®. 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 KEYTRUDA®) 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. You should not place undue reliance on these statements, or the scientific data presented. Forward-looking statements are often identified by terms such as “will”, “may”, “should”, “anticipate”, “expect”, “believe”, “seek”, “potentially” and similar expressions. and are subject to risks and uncertainties. Forward-looking statements are based on a number of assumptions believed by the Company to be reasonable at the date of this news release. Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, there can be no assurance that such statements will prove to be accurate. These statements are subject to certain risks and uncertainties and may be based on assumptions that could cause actual results and future events to differ materially from those anticipated or implied in such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include the risks detailed in the latest annual information form of the Company and in other filings made by the Company with the applicable securities regulators from time to time in Canada. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management, may prove to be incorrect and actual results may differ materially from those anticipated or implied in forward-looking statements. 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 Daniel ScarrInvestor Relations & Business Developmentdscarr@medicenna.com(647) 220-4509

Clinical ResultImmunotherapyPhase 2Orphan DrugRadiation Therapy

29 Nov 2024

·www.globenewswire.com

Updated MDNA11 Monotherapy and Combination Clinical Data from the Ongoing Phase 1/2 ABILITY-1 Study to be Presented at the 2024 Immunotherapy Bridge Conference

Nov. 27, 2024 -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA, OTCQX: MDNAF), a clinical-stage immunotherapy company focused on the development of Superkines, announced today that updated clinical data from the ongoing Phase 1/2 ABILITY-1 study will be presented as part of an oral podium presentation at the 2024 Immunotherapy Bridge Conference, taking place from December 4-5, 2024 in Naples, Italy. The oral presentation will include updated clinical data from the monotherapy and combination arms of the ongoing Phase 1/2 ABILITY-1 Study evaluating MDNA11, a long-acting ‘beta-enhanced not-alpha’ interleukin-2 (“IL-2”) super-agonist, in patients with advanced or metastatic solid tumors. Title: Updated Safety and Efficacy Results from the First-in-Human Study of MDNA11 (ABILITY-1), a Next Generation ‘Beta-Enhanced Not-Alpha’ IL-2 Superkine, Show Single-Agent Activity in Patients with Advanced Solid Tumors Presentation Date: Thursday, December 5, 2024 8:45 AM CET (2:30 AM EST) Presenter: Dr. Arash Yavari, MBBS, DPhil; Director of Clinical Strategy Following the presentation, a copy of the presentation will be available on the “Scientific Presentations” page of Medicenna’s website. 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 pembrolizumab. 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 pembrolizumab. In the combination dose escalation portion of the Phase 2 study, approximately 20 patients are expected to be enrolled and administered ascending doses of MDNA11 intravenously in combination with pembrolizumab. This portion of the study includes patients with a wide range of solid tumors with the potential for susceptibility to immune modulating therapeutics. Upon identification of an appropriate dose regimen for combination, the study will proceed to a combination dose expansion cohort. 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 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. The content above comes from the network. if any infringement, please contact us to modify.

ImmunotherapyOrphan DrugClinical Result

27 Nov 2024

·aulosbio.com

Aulos Bioscience Doses First Patient in Phase 2 Cohort Evaluating the Combination of Avelumab and AU-007 for the Treatment of Non-Small Cell Lung Cancer

Press Releases In the News Media Inquiries Videos LARKSPUR, Calif., November 27, 2024 – Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of potentially best-in-class IL-2 therapeutics, today announced dosing of the first patient with AU-007, avelumab, a PD-L1 antibody with Fc effector function, and low-dose, subcutaneous aldesleukin in a Phase 2 cohort focused on the second-line treatment of PD-L1+ non-small cell lung cancer (NSCLC). The Phase 2 cohort is a clinical trial collaboration with Ares Trading S.A., a Swiss subsidiary of Merck KGaA, Darmstadt, Germany, and part of Aulos’ Phase 1/2 clinical trial of AU-007. “We are excited to move forward with evaluating this combination therapy in a clinical setting after seeing encouraging synergy with AU-007 and a surrogate model of avelumab in preclinical studies including complete elimination of established solid tumors,” said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer. “Avelumab’s profile, coupled with AU-007 and low-dose, subcutaneous aldesleukin, could potentially offer a new therapeutic option for patients with advanced or metastatic PD-L1+ non-small cell lung cancer that has progressed following first-line therapy with a checkpoint inhibitor. We thank Merck KGaA, Darmstadt, Germany, the patients and the clinical trial investigators who have chosen to participate in this clinical trial.” In May, Aulos announced a collaboration and supply agreement with Ares Trading S.A., a Swiss subsidiary of Merck KGaA, Darmstadt, Germany, for use of avelumab in combination with AU-007 and low-dose, subcutaneous aldesleukin in an additional Phase 2 cohort of the AU-007 Phase 1/2 clinical trial. Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody approved for use in multiple tumor types. Avelumab is the only approved PD-L1 or PD-1 antibody with Fc effector function, and has been shown in vitro to engage natural killer (NK) cells to kill tumor cells by a process known as antibody-dependent cellular cytotoxicity (ADCC), while also interrupting the PD-1/PD-L1 pathway that inhibits effector T cell (Teff) function. AU-007 is the first human IgG1 monoclonal antibody designed by leveraging artificial intelligence to enter a human clinical trial. In preclinical studies, strong anti-cancer activity, including complete tumor eradications, was observed when AU-007 was dosed with a single loading dose of human interleukin-2 (hIL-2) and an anti-PD-L1 surrogate of avelumab. The AU-007 Phase 1/2 study is currently enrolling patients with unresectable locally advanced or metastatic cancer at multiple clinical trial site locations in the United States and Australia. Positive Phase 1 and preliminary Phase 2 data presented at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting earlier this month shows evidence of AU-007’s anti-tumor activity. Preliminary Phase 2 data reveal that a combination of AU-007 and low-dose, subcutaneous aldesleukin is clinically active in melanoma. Additionally, data from all 77 patients show durable Treg reduction – a compelling result in the IL-2 class – and correlated progression-free survival. Aulos plans to share preliminary data from the Phase 2 cohort studying AU-007 with avelumab and low-dose, subcutaneous aldesleukin as a second-line treatment for PD-L1+ NSCLC in the first half of 2025. 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. To learn more about the AU-007 Phase 1/2 clinical trial program, including study locations in the United States and Australia, please visit ClinicalTrials.gov (identifier: NCT05267626), www.solidtumorstudy.com (U.S.) and www.solidtumourstudy.com (Australia). About Aulos Aulos Bioscience is an immuno-oncology company working to revolutionize cancer patient care through best-in-class IL-2 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 field of artificial intelligence, antibody development and cancer immunotherapies. For more information, visit www.aulosbio.com, X (@AulosBioscience) and LinkedIn. Contact: info@aulosbio.com Media inquiries: Mike Beyer, Sam Brown Inc. / 312-961-2502 / mikebeyer@sambrown.com

Phase 2ImmunotherapyDrug ApprovalASCO

100 Deals associated with Aldesleukin

External Link

KEGG	Wiki	ATC	Drug Bank
D00748	-	L03AC01	DB00041

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Renal Cell Carcinoma	US	Chiron Corp.	05 May 1992

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
High Risk Neuroblastoma	Phase 3	US	National Cancer Institute	21 Dec 2009
Refractory Hodgkin Lymphoma	Phase 3	US	National Cancer Institute	01 Nov 2003
Refractory Hodgkin Lymphoma	Phase 3	AU	National Cancer Institute	01 Nov 2003
Refractory Hodgkin Lymphoma	Phase 3	CA	National Cancer Institute	01 Nov 2003
Neuroblastoma recurrent	Phase 3	US	National Cancer Institute	18 Oct 2001
Neuroblastoma recurrent	Phase 3	AU	National Cancer Institute	18 Oct 2001
Neuroblastoma recurrent	Phase 3	CA	National Cancer Institute	18 Oct 2001
Neuroblastoma recurrent	Phase 3	NZ	National Cancer Institute	18 Oct 2001
Neuroblastoma recurrent	Phase 3	PR	National Cancer Institute	18 Oct 2001
Acute Basophilic Leukemia	Phase 3	US	National Cancer Institute	01 Nov 2000

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03318900 (CTgov)	Phase 1/2	Recurrent ovarian cancer \| Platinum-Resistant Ovarian Carcinoma	5	Cyclophosphamide+IL-2 (Dose Level 1)	rdgrfndoca(eycjdlmtzn) = ukyfrezhlf xtdtmnoend (oyqrehalij, gybmdsxhwt - qfspujhnbj) View more	-	07 Nov 2024
				Cyclophosphamide+IL-2 (Dose Level 2)	rdgrfndoca(eycjdlmtzn) = vygnooinlq xtdtmnoend (oyqrehalij, lrbtvgpcft - qpyjxvqwxr) View more
NCT05267626 (SITC2024) Manual	Phase 1/2	Advanced Malignant Solid Neoplasm	-	AU-007	zfyfbleqkz(tkzftshqqw) = None bpzwmojhwj (qmymozttqr ) View more	Positive	05 Nov 2024
				AU-007 + aldesleukin
NCT02027935 (CTgov)	Phase 2	Metastatic melanoma	16	Autologous CD8+ Melanoma Specific T Cells+ipilimumab+Cyclophosphamide+Aldesleukin	xftzrimnzb(vwmskxqcjk) = vlrhsrnqoi ujewveakoh (fxvnznltow, qhayvyzuyg - utdisnlfft) View more	-	08 Oct 2024
NCT03007238 (CTgov)	Phase 2	Chronic graft-versus-host disease \| Steroid Refractory Graft Versus Host Disease	10	ECP (Treatment (ECP+IL-2))	dryaafrzmm(grvkwxfbdl) = zukdrizpdb nfhcfypvtk (ewytfmxjog, gddwmrcbxm - ukqefwtohd) View more	-	08 Apr 2024
				ECP (Overall Study)	hxmppgdtwi(cdfakcwhln) = phkuytepmc zxuscasfcj (gpxksykpcq, ultfegmpfu - piebigsdzn) View more
NCT01856023 (PROCLIVITY02, CTgov)	Phase 4	Metastatic melanoma	29	ipilimumab+High Dose Interleukin-2 (Treatment Arm 1)	vuhbomoagy(meuyjgqxrx) = zjedhpxsng fkgywopkmg (orwxrxkppk, htdlmbbxml - tpkacewchx)	-	05 Dec 2023
				ipilimumab+High Dose Interleukin-2 (Treatment Arm 2)	vuhbomoagy(meuyjgqxrx) = bqeldwfrbv fkgywopkmg (orwxrxkppk, zqmzwxgkaa - olxlmprsdr)
NCT02620865 (CTgov)	Phase 1/2	Pancreatic adenocarcinoma metastatic \| Advanced Pancreatic Adenocarcinoma	2	Laboratory Biomarker Analysis+Paclitaxel Albumin-Stabilized Nanoparticle Formulation+Leucovorin Calcium+Gemcitabine Hydrochloride+Sargramostim+Aldesleukin+Oxaliplatin+Irinotecan Hydrochloride+fluorouracil	fdixmematg(dydssvxdgg) = vrimztziqf ubebuscdpc (tzjhxrtfhu, fwiaxwshva - gabaxdpccj) View more	-	15 May 2023
NCT02748564 (CTgov)	Phase 2	Melanoma, Cutaneous Malignant \| Mucosal Melanoma of the Head and Neck \| Metastatic melanoma ... View more	10	Laboratory Biomarker Analysis+pembrolizumab+Aldesleukin	nmgsiffisz(ckcnoyjavk) = dmfioblwyn wvydbbwlva (gfawwlvxhj, fradqthkco - kgcmyborfs) View more	-	09 Feb 2023
Tandem Meetings ASTCT and CIBMTR2023	Not Applicable	Steroid Refractory Graft Versus Host Disease	15	Low Dose Interleukin-2 (LD IL-2)	uiuhevkmcz(suvwvwefzd) = Two deaths occurred; one patient with advanced hepatic dysfunction due to cGVHD and one patient with poor graft function at the time of IL-2 start iycxjcsdxz (reyimjieqr ) View more	Positive	01 Feb 2023
LITE trial (EASL2022)	Phase 4	Maintenance CD4+CD25+Foxp3+	6	Low dose interleukin-2 (LDIL-2)	aevvcfalbh(idztndephm) = The trial was terminated after the first six trial participants failed to reach the primary end point due to rejection requiring immunosuppression reinstitution pzznzlzngj (iazwribpvm ) View more	Negative	25 Jun 2022
NCT03113773 (Pubmed) Manual	Phase 1/2	Myocardial Ischemia	41	Proleukin	ppfasazlfj(daavobrtzt) = The majority of adverse events were mild. gerikheyso (mrkkjijzix ) View more	Positive	09 Jan 2022
				Placebo

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis