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Last update 23 Jan 2025

Aldesleukin

Last update 23 Jan 2025

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+ [8]

Active Indication

Renal Cell CarcinomaNeuroblastoma recurrentMalignant melanoma, metastatic+ [30]

Inactive Indication

Acquired Immunodeficiency SyndromeAcute Basophilic LeukemiaAcute Eosinophilic Leukemia+ [113]

Originator Organization

Chiron Corp.

Active Organization

National Cancer Institute

National Institutes of Health

Prometheus Laboratories, Inc.

+ [7]

Inactive Organization

National Institutes of Health Clinical Center

Barbara Ann Karmanos Cancer Institute

National Institute on Aging

Drug Highest PhaseApproved

First Approval Date

US (05 May 1992),

Renal Cell Carcinoma

RegulationOrphan Drug (US), Orphan Drug (KR)

Structure/Sequence

Sequence Code 720

Source: *****

413

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 Date27 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]

NCT05989828

/ RecruitingPhase 1IIT

Phase Ib Clinical Trial of Autologous Anti-NY-ESO-1 TCR-Engineered T Cells in Patients With Relapsed/Refractory Locally Advanced or Metastatic NY-ESO-1-Expressing Triple Negative Breast Cancer

This phase Ib trial tests the safety, side effects and best dose of anti-HLA-A2/NY-ESO-1 T-cell receptor (TCR)-transduced autologous T lymphocytes (A2-ESO-1 TCR-T cells) in treating patients with NY-ESO-1 overexpression positive triple negative breast cancer (TNBC) that has come back after a period of improvement (relapsed/recurrent) or that does not respond to treatment (refractory), and that may have spread from where it first started (primary site) to nearby tissue, lymph nodes (advanced) or to other places in the body (metastatic). NY-ESO-1 is an antigen found on the surface of many different types of tumor cells including TNBC. Antigens make it possible for immune cells to recognize and kill germ cells that invade the body, however, it is more difficult for immune cells to recognize antigens on tumor cells. T cells are a special type of immune cell in the blood. These T cells may be trained to recognize the NY-ESO-1 antigen on tumor cells, allowing the T cells to attack and kill those tumor cells. The A2-ESO-1 TCR-T cells are T cells that have been removed from the patient's blood through a process called leukapheresis and then changed in the laboratory to recognize NY-ESO-1 on tumor cells. When given back to the patient, these A2-ESO-1 TCR-T cells find and attack tumor cells that express NY-ESO-1. Chemotherapy drugs, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. They are given before the T cells to support optimum activity of the A2-ESO-1 TCR-T cells. IL-2 (aldesleukin) is in a class of drugs known as cytokines. It is a man-made version of a naturally occurring protein that stimulates the body to produce other chemicals which increase the body's ability to fight cancer. A2-ESO-1 TCR-T cells may kill more tumor cells in patients with recurrent or refractory advanced or metastatic TNBC that overexpresses NY-ESO-1.

Start Date17 Dec 2024

Sponsor / Collaborator

University of Southern California

[+1]

100 Clinical Results associated with Aldesleukin

100 Translational Medicine associated with Aldesleukin

100 Patents (Medical) associated with Aldesleukin

3,038

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 ; Richter, Kirsten ; Huber, Christoph ; 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.

09 Dec 2024·Journal of Immunotoxicology

Revival of recombinant IL-2 therapy – approaches from the past until today

Review

Author: Roser, Luise A. ; Ortega Iannazzo, Samira ; Sakellariou, Christina ; Gogesch, Patricia ; Sommer, Charline ; Waibler, Zoe

Interleukin-2 (IL-2) was one of the first cytokines discovered and its central role in T cell function soon led to the notion that the cytokine could specifically activate immune cells to combat cancer cells. Recombinant human IL-2 (recIL-2) belonged to the first anti-cancer immunotherapeutics that received marketing authorization and while it mediated anti-tumor effects in some cancer entities, treatment was associated with severe and systemic side effects. RecIL-2 holds an exceptional therapeutic potential, which can either lead to stimulation of the immune system - favorable during cancer treatment - or immunosuppression - used for treatment of inflammatory diseases such as autoimmunity. Due to these pleiotropic immune effects, recIL-2 therapy is still a hot topic in research and modified recIL-2 drug candidates show ameliorated efficacy and safety in pre-clinical and clinical studies. The Immune Safety Avatar (imSAVAR) consortium aims to systemically assess mechanisms leading to adverse events provoked by recIL-2 immunotherapy as a use case in order to aid safety evaluation of future recIL-2-based therapies. Here, we summarize the historical use of recIL-2 therapy, associated side effects, and describe the molecular basis of the dual role of IL-2. Finally, an overview of new recIL-2 compounds and delivery systems, which are currently being developed, will be given, highlighting a possible comeback of recIL-2 therapy.

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.

News (Medical) associated with Aldesleukin

17 Jan 2025

·www.globenewswire.com

Iovance Biotherapeutics Reports Inducement Grants under NASDAQ Listing Rule 5635(c)(4)

SAN CARLOS, Calif., Jan. 17, 2025 (GLOBE NEWSWIRE) -- Iovance Biotherapeutics, Inc. (NASDAQ: IOVA) ("Iovance" or the “Company”), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (“TIL”) therapies for patients with cancer, today announced that on January 16, 2025 (the “Date of Grant”), the Company approved the grant of inducement stock options covering an aggregate of 224,550 shares of Iovance’s common stock to forty-one new, non-executive employees. The awards were granted under Iovance’s Amended and Restated 2021 Inducement Plan, which was adopted on September 22, 2021 and amended and restated on January 12, 2022, March 13, 2023, February 26, 2024, and November 22, 2024 and provides for the granting of equity awards to new employees of Iovance by the Company’s compensation committee in accordance with Nasdaq Listing Rule 5635(c)(4). Each of the stock options granted as referenced in this press release has an exercise price of $5.76, the closing price of Iovance’s common stock on the Date of Grant. Each stock option vests over a three-year period, with one-third of the shares vesting on the first anniversary of the employee’s start date (the “First Vesting Date”) and the remaining shares vesting in eight quarterly installments over the next two years, commencing with the first quarter following the First Vesting Date, subject to continued employment with the Company through the applicable vesting dates. About Iovance Biotherapeutics, Inc. Iovance Biotherapeutics, Inc. aims to be the global leader in innovating, developing, and delivering tumor infiltrating lymphocyte (TIL) therapies for patients with cancer. We are pioneering a transformational approach to cure cancer by harnessing the human immune system’s ability to recognize and destroy diverse cancer cells in each patient. The Iovance TIL platform has demonstrated promising clinical data across multiple solid tumors. Iovance’s Amtagvi® is the first FDA-approved T cell therapy for a solid tumor indication. We are committed to continuous innovation in cell therapy, including gene-edited cell therapy, that may extend and improve life for patients with cancer. For more information, please visit www.iovance.com. Amtagvi® and its accompanying design marks, Proleukin®, Iovance®, and IovanceCares™ are trademarks and registered trademarks of Iovance Biotherapeutics, Inc. or its subsidiaries. All other trademarks and registered trademarks are the property of their respective owners. Forward-Looking Statements Certain matters discussed in this press release are “forward-looking statements” of Iovance Biotherapeutics, Inc. (hereinafter referred to as the “Company,” “we,” “us,” or “our”) within the meaning of the Private Securities Litigation Reform Act of 1995 (the “PSLRA”). Without limiting the foregoing, we may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “forecast,” “guidance,” “outlook,” “may,” “can,” “could,” “might,” “will,” “should,” or other words that convey uncertainty of future events or outcomes and are intended to identify forward-looking statements. Forward-looking statements are based on assumptions and assessments made in light of management’s experience and perception of historical trends, current conditions, expected future developments, and other factors believed to be appropriate. Forward-looking statements in this press release are made as of the date of this press release, and we undertake no duty to update or revise any such statements, whether as a result of new information, future events or otherwise. Forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties, and other factors, many of which are outside of our control, that may cause actual results, levels of activity, performance, achievements, and developments to be materially different from those expressed in or implied by these forward-looking statements. Important factors that could cause actual results, developments, and business decisions to differ materially from forward-looking statements are described in the sections titled "Risk Factors" in our filings with the U.S. Securities and Exchange Commission, including our most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q, and include, but are not limited to, the following substantial known and unknown risks and uncertainties inherent in our business: the risks related to our ability to successfully commercialize our products, including Amtagvi, for which we have obtained U.S. Food and Drug Administration (“FDA”) approval, and Proleukin, for which we have obtained FDA and European Medicines Agency (“EMA”) approval; the risk that the EMA or other ex-U.S. regulatory authorities may not approve or may delay approval for our marketing authorization application submission for lifileucel in metastatic melanoma; the acceptance by the market of our products, including Amtagvi and Proleukin, and their potential pricing and/or reimbursement by payors, if approved (in the case of our product candidates), in the U.S. and other international markets and whether such acceptance is sufficient to support continued commercialization or development of our products, including Amtagvi and Proleukin, or product candidates, respectively; future competitive or other market factors may adversely affect the commercial potential for Amtagvi or Proleukin; the risk regarding our ability or inability to manufacture our therapies using third party manufacturers or at our own facility, including our ability to increase manufacturing capacity at such third party manufacturers and our own facility, may adversely affect our commercial launch; the results of clinical trials with collaborators using different manufacturing processes may not be reflected in our sponsored trials; the risk regarding the successful integration of the recent Proleukin acquisition; the risk that the successful development or commercialization of our products, including Amtagvi and Proleukin, may not generate sufficient revenue from product sales, and we may not become profitable in the near term, or at all; the risks related to the timing of and our ability to successfully develop, submit, obtain, or maintain FDA, EMA, or other regulatory authority approval of, or other action with respect to, our product candidates; whether clinical trial results from our pivotal studies and cohorts, and meetings with the FDA, EMA, or other regulatory authorities may support registrational studies and subsequent approvals by the FDA, EMA, or other regulatory authorities, including the risk that the planned single arm Phase 2 IOV-LUN-202 trial may not support registration; preliminary and interim clinical results, which may include efficacy and safety results, from ongoing clinical trials or cohorts may not be reflected in the final analyses of our ongoing clinical trials or subgroups within these trials or in other prior trials or cohorts; the risk that enrollment may need to be adjusted for our trials and cohorts within those trials based on FDA and other regulatory agency input; the risk that the changing landscape of care for cervical cancer patients may impact our clinical trials in this indication; the risk that we may be required to conduct additional clinical trials or modify ongoing or future clinical trials based on feedback from the FDA, EMA, or other regulatory authorities; the risk that our interpretation of the results of our clinical trials or communications with the FDA, EMA, or other regulatory authorities may differ from the interpretation of such results or communications by such regulatory authorities (including from our prior meetings with the FDA regarding our non-small cell lung cancer clinical trials); the risk that clinical data from ongoing clinical trials of Amtagvi will not continue or be repeated in ongoing or planned clinical trials or may not support regulatory approval or renewal of authorization; the risk that unanticipated expenses may decrease our estimated cash balances and forecasts and increase our estimated capital requirements; the risk that we may not be able to recognize revenue for our products; the risk that Proleukin revenues may not continue to serve as a leading indicator for Amtagvi revenues; the risks regarding our anticipated operating and financial performance, including our financial guidance and projections; the effects of global pandemic; the effects of global and domestic geopolitical factors; and other factors, including general economic conditions and regulatory developments, not within our control. Any financial guidance provided in this press release assumes the following: no material change in our ability to manufacture our products; no material change in payor coverage; no material change in revenue recognition policies; no new business development transactions not completed as of the period covered by this press release; and no material fluctuation in exchange rates.

Drug ApprovalClinical ResultCell Therapy

07 Jan 2025

·www.prnewswire.com

Norgine submits Marketing Authorisation Application to the European Medicines Agency for eflornithine (difluoromethylornithine [DFMO]) in high-risk neuroblastoma

Back to media releases Next media release LONDON, Jan. 7, 2025 /PRNewswire/ -- Norgine today announced that it completed its marketing authorisation application filing to European Medicines Agency (EMA) for eflornithine in high-risk neuroblastoma (HRNB). This follows the submissions in April 2024, via Project Orbis, in Australia, Switzerland and the United Kingdom. This milestone further supports Norgine's efforts to give patients access to eflornithine and bring a further treatment option in the field of paediatric oncology. Norgine and USWM, LLC (dba US WorldMeds), a Kentucky-based specialty pharmaceutical company, have an exclusive licensing agreement by which Norgine will register and commercialise eflornithine, also referred to as DFMO, in Europe, Australia and New Zealand. On 13 December 2023, the US Food and Drug Administration (FDA) approved eflornithine as the first oral maintenance therapy for HRNB, indicated to reduce the risk of relapse in adult and paediatric patients who have received certain prior therapies.[1] The approval decision was based on findings from a trial comparing outcomes from patients treated with eflornithine in Study 3b (NCT02395666)[2],[4] to control patients derived from Study ANBL0032 (NCT00026312; clinical-trial-derived external control arm)[3],[4]. The study with eflornithine treated patients showed improved event-free survival and overall survival when compared to outcomes for patients with HRNB treated with the standard of care (SoC).[1] Dr David Gillen, Chief Medical Officer at Norgine, added, "This submission via the EU Centralised Procedure represents another important step in the regulatory process for eflornithine and further emphasises Norgine's passion and commitment in attempting to secure additional treatment options for patients living with HRNB, a condition with a high level of unmet medical need." Janneke van der Kamp, CEO of Norgine added "Submitting this marketing authorisation to the EMA marks a pivotal step for patients facing this challenging cancer. We are committed to advancing innovative therapies that address the unmet needs of young patients and their families, and this milestone brings us closer to offering hope where it's most needed". Follow @norgine Notes to Editors: HRNB background Children diagnosed with HRNB undergo an intense SoC regimen that still leaves them vulnerable to relapse and death, a risk that is highest for the first two years after completing treatment.[5] Approximately 30% of patients who attain remission following upfront therapy will relapse, and once relapsed, mortality significantly increases with a post-relapse 4-year overall survival of under 10%.[5], [6] Therefore, avoiding relapse is key to long-term survival, yet outside of the United States there are no approved therapies for sustaining remission following SoC treatment. The data demonstrate that using eflornithine after completion of upfront SoC treatment, as post-maintenance therapy extends remission and reduces risk of relapse in patients with HRNB. About Norgine Norgine is a uniquely positioned, specialty pharmaceutical and consumer healthcare company, with over €500 million of annual revenues and a 120-year track record of bringing life-changing products to patients and consumers across our core markets of Western Europe, Australia and New Zealand. Our integrated approach – strong commercial capabilities, deep medical, regulatory and clinical expertise, in-house manufacturing, robust supply networks, and best in class enabling functions – ensures that we can deliver high-quality, transformative medicines quickly and effectively to over 25 million patients annually. Today's Norgine is a nimble, innovative, and high-performing company that has been transformed by a relentless focus on operational excellence. This focus will enable us to secure the legacy of more than a century of innovation and doing the right thing by our patients, as we push the boundaries and take strides into new therapeutic areas. NORGINE and the sail logo are trademarks of the Norgine group of companies. References FDA approves eflornithine for adult and pediatric patients with high-risk neuroblastoma. FDA. News release. 13 December 2023. Available from: FDA approves eflornithine for adult and pediatric patients with high-risk neuroblastoma | FDA Clinical Trial NCT02395666; Preventative trial of difluoromethylornithine (DFMO) in high risk patients with neuroblastoma that is in remission. Available from: Study Details | Preventative Trial of Difluoromethylornithine (DFMO) in High Risk Patients With Neuroblastoma That is in Remission | ClinicalTrials.gov. Clinical Trial NCT00026312; Isotretinoin with or without dinutuximab,[1] aldesleukin, and sargramostim following stem cell transplant in treating patients with neuroblastoma. Available from: Study Details | Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma | ClinicalTrials.gov Oesterheld J, Ferguson W, Kraveka JM, Bergendahl G, Clinch T, Lorenzi E et al. Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma: Externally Controlled, Propensity Score-Matched Survival Outcome Comparisons. 2024; 42 (1): 90-102. Basta NO, Halliday GC, Makin G, Birch J, Feltbower R, Bown N, et al. Factors associated with recurrence and survival length following relapse in patients with neuroblastoma. Br J Cancer. 2016;115:1048-57. London WB, Bagatell R, Weigel BJ, Fox E, Guo D, Van Ryn C, et al. Historical time to disease progression and progression-free survival in patients with recurrent/refractory neuroblastoma treated in the modern era on Children's Oncology Group early-phase trials. Cancer. 2017;123:4914-23.[2] Job code: UK-ONC-NP-2400019 Logo - WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

License out/inDrug Approval

13 Dec 2024

·www.globenewswire.com

Medicenna Presents Preclinical Data on MDNA11 as First Step to Shrink Tumors Before Surgery and Prevent Metastasis at the 2024 San Antonio Breast Cancer Symposium (SABCS)

Single-agent MDNA11 was more effective than a combination of immune checkpoint inhibitors (anti-mPD1 and anti-mCTLA4) in preventing metastasis and achieving long-term survival in an aggressive mouse model of triple negative breast cancer (TNBC) Mice treated with MDNA11 prior to surgery were able to mount powerful immune and memory response to subsequent tumor rechallenges, demonstrating potential to prevent new tumor growth TORONTO and HOUSTON, Dec. 13, 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 new preclinical data on MDNA11 was presented at the 2024 San Antonio Breast Cancer Symposium (SABCS), the world’s largest breast cancer conference, taking place from December 10-13, 2024, in San Antonio, Texas. Metastasis is the leading cause of cancer-related deaths worldwide. 1 in 8 women will be diagnosed with breast cancer in the US and 1 in 3 of those will become metastatic resulting in approximately 42,000 breast cancer deaths every year. Of those deaths, it is estimated that 97-99% of those will be from metastatic breast cancer.1 Among breast cancer subtypes, triple-negative breast cancer (TNBC) is particularly aggressive, spreading more rapidly and representing a significant unmet medical need. Neoadjuvant immunotherapy offers a promising treatment strategy in which patients with advanced but resectable cancer receive immunotherapy before surgery. This approach aims to shrink tumors, making them easier to remove, delay or prevent metastasis, while also targeting cancerous tissue that may not yet be detectable. Additionally, immunotherapy can prime the immune system against tumor antigens, promoting the development of long-lasting anti-cancer T cells. These T cells may help protect against residual tumor cells that could re-emerge and drive metastatic disease. The presentation at 2024 SABCS highlighted the potential of MDNA11, a long-acting ‘β-enhanced not-α’ IL-2 Superkine, to improve treatment outcomes when administered prior to surgery. New findings demonstrated that a single low dose of MDNA11 as a neoadjuvant therapy significantly prevented metastasis, extended survival, and enabled a memory immune response that protects against tumor rechallenges in a TNBC model. “We are impressed by MDNA11’s remarkable capability, in the on-going ABILITY-1 clinical trial, to durably control cancer in patients with advanced late-stage metastatic disease in immunotherapy resistant tumors. This naturally encourages us to evaluate the potential of MDNA11 to tackle cancer head-on at the earlier stages of the disease and reverse cancer from a death sentence to a chronic manageable condition,” said Fahar Merchant, PhD, President and CEO of Medicenna. “Our findings show that MDNA11 alone not only prevents metastasis in an aggressive preclinical breast cancer model when administered as a single pre-treatment prior to surgery, but also delivers superior long-term survival by preventing metastasis when compared to combinations of the leading checkpoint inhibitors, such as anti-CTLA4 and anti-PD-1. These data illustrate MDNA11’s potential to redefine traditional immunotherapy by attacking cancer at its earliest stages and efficiently leverage the patient’s healthier immune status to dramatically improve patient outcomes.” Key findings from presentation of MDNA11 pre-treatment prior to surgery in the aggressive TNBC model included: Metastasis Prevention: A single dose of neoadjuvant MDNA11 prevented the spread of tumors, with vast majority of treated mice (7/8 at high-dose of 5 mg MDNA11/kg and 6/7 at low-dose of 2 mg MDNA11/kg) surviving to study end (>4 months) without signs of metastasis despite tumor rechallenges. By contrast, all mice in the control group developed multiple metastasis and died within ~2 months even after tumor resection surgery.Superior to Checkpoint Inhibitors: MDNA11 alone, even at the lower dose, was more effective than a combination of immune checkpoint inhibitors (anti-mPD1 and anti-mCTLA4) in preventing metastasis and achieving long-term survival.Memory Response Against Tumor Rechallenge: Mice treated with MDNA11 were able to mount strong immune response to subsequent tumor rechallenges by engaging tumor antigen-specific T cells, demonstrating protection against new tumor growth.Immune Cell Activation: MDNA11 promoted the infiltration of CD8+ T cells with potent tumor-killing capacity (GrzB+) into the tumor microenvironment (TME) with no impact on immune-suppressive Treg cells, driving a potent and lasting immune response. 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 pembrolizumab. 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 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 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. 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 & Corporate Developmentdscarr@medicenna.com(647) 220-4509 1 Metastatic breast cancer statistics, METAvivor. https://www.metavivor.org/mbc-prep/metastatic-breast-cancer-statistics

ImmunotherapyOrphan DrugPhase 2Clinical Result

100 Deals associated with Aldesleukin

External Link

KEGG	Wiki	ATC	Drug Bank
D00748	-	L03AC01	DB00041

R&D Status

Approved

10 top approved records.

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

Developing

10 top R&D records.

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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

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02500576 (CTgov)	Phase 2	Melanoma, Cutaneous Malignant \| Metastatic melanoma	18	I2+fludarabine+cyclophosphamide+MK-3475 (Arm 1)	lsdzdmosag(kqavsdmxzj) = derkqbkani lepfjdsyxm (vkgixvhksq, lmhvvbemah - bcusxpfyuq) View more	-	15 Jan 2025
				TIL+fludarabine+cyclophosphamide+MK-3475+IL-2 (Arm 2)	lsdzdmosag(kqavsdmxzj) = rzfnscjtov lepfjdsyxm (vkgixvhksq, txxliusjhg - hjcdatbyyo) View more
NCT03318900 (CTgov)	Phase 1/2	Recurrent ovarian cancer \| Platinum-Resistant Ovarian Carcinoma	5	IL-2+Cyclophosphamide (Dose Level 1)	hdozjntadq(wbxtcnsxgt) = hqqfpxmvon yfdytzmdun (bvgkpyypib, akgcvihwvj - ujdturtvaa) View more	-	07 Nov 2024
				IL-2+Cyclophosphamide (Dose Level 2)	hdozjntadq(wbxtcnsxgt) = prcjahhtet yfdytzmdun (bvgkpyypib, zhirkxjynw - xjjuqklrkd) View more
NCT05267626 (SITC2024) Manual	Phase 1/2	Advanced Malignant Solid Neoplasm	-	AU-007	nveclwluuf(gbdyppessb) = None ynizyznufv (tjuomgmrjm ) View more	Positive	05 Nov 2024
				AU-007 + aldesleukin
NCT03296137 (2017-002323-25 \| ###DELETE, CTgov)	Phase 1/2	Neoplasms	25	infiltrating lymphocytes+Fludara+Cyclophosphamide+proleukin (All Participants)	tppowvalss(qzisnlzmqi) = vojajfzgoq gwxxdhlqhv (njzuemrptq, vubukgvsqd - pkpspgxgpn) View more	-	26 Oct 2024
				infiltrating lymphocytes+Fludara+Cyclophosphamide+proleukin (Treated Participants)	yhgffdmkan(vdlvbauscl) = fozepcdlhs iscneqxhil (vzdtrpfrxc, iltpqxjgdi - lklqfemlxg) View more
NCT02027935 (CTgov)	Phase 2	Metastatic melanoma	16	Autologous CD8+ Melanoma Specific T Cells+ipilimumab+Cyclophosphamide+Aldesleukin	pqxglbzyli(xmhcpmxgro) = fyxqjfmuze xdyvdycgjx (emokwdczgy, konnmkxizo - updhiskqzs) View more	-	08 Oct 2024
NCT03233828 (IL-2, CTgov)	Phase 3	Melanoma, Cutaneous Malignant \| Visible Lesion	1	Aldesleukin (Intralesional IL-2 Injection)	ebswabcnhq(srrwekfkoz) = ihjzhhhvrn xccpzktdee (rmiziqaovq, bjunsoumrg - xgisstoatt) View more	-	24 Jul 2024
				Saline (Saline Injection)	ebswabcnhq(srrwekfkoz) = tfddprhiwp xccpzktdee (rmiziqaovq, uxtmsofetn - njltjskrjl) View more
NCT03007238 (CTgov)	Phase 2	Chronic graft-versus-host disease \| Steroid Refractory Graft Versus Host Disease	10	ECP (Treatment (ECP+IL-2))	tmpxczsppu(mwkfqqszen) = icagwvhedu rtvytomjov (ayqmigvqtr, askbeknboo - hvcisjizpy) View more	-	08 Apr 2024
				ECP (Overall Study)	ttgwfzstzu(tvtqazvfac) = ewbeoxfabl tkwsmguslq (lxhdpqskox, yvtagrpifv - jiwaqtkami) View more
NCT01856023 (PROCLIVITY02, CTgov)	Phase 4	Metastatic melanoma	29	ipilimumab+High Dose Interleukin-2 (Treatment Arm 1)	napiaxmclu(zplcxpidet) = smvtpkxdam bhfvvjuawt (rnjxdlrhed, anjyteubce - cpgguqtidf)	-	05 Dec 2023
				ipilimumab+High Dose Interleukin-2 (Treatment Arm 2)	napiaxmclu(zplcxpidet) = dbhslifgxj bhfvvjuawt (rnjxdlrhed, zglpyifqnr - pljhqnhfqu)
NCT02620865 (CTgov)	Phase 1/2	Pancreatic adenocarcinoma metastatic	2	Laboratory Biomarker Analysis+Paclitaxel Albumin-Stabilized Nanoparticle Formulation+Leucovorin Calcium+Gemcitabine Hydrochloride+Sargramostim+Aldesleukin+Oxaliplatin+Irinotecan Hydrochloride+fluorouracil	ymgiarksqr(tvpityxwgv) = hwbzbxsmnl njyzepfejw (awtwvditsw, fzkpvkxzpu - xsxlknvauo) 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	dqqnvfmxny(zrvsteztkr) = vtpfqbjkww jjnpsjddpg (csnnaksczq, exemqirsnh - xzqspmfusw) View more	-	09 Feb 2023

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