Last update 21 Nov 2024

Aldesleukin

Last update 21 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Interleukins

Synonyms

125-L-Serine-2-133-interleukin 2, Aldesleukin(重组人白介素-2), IL-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+ [83]

Originator Organization

Chiron Corp.

Active Organization

National Institutes of Health

National Cancer InstituteBoehringer Ingelheim Pharma GmbH & Co., KG

+ [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 (US)

Gene Sequence

Sequence Code 720

Source: *****

427

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

3,027

Literatures (Medical) associated with Aldesleukin

01 Nov 2024·Rheumatology

Where are we now in biologic drugs for myositis?

Review

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

AbstractIdiopathic 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.

15 Oct 2024·The Journal of Immunology

Cutting Edge: Low-dose Recombinant IL-2 Treatment Prevents Autoantibody Responses in Systemic Lupus Erythematosus via Regulatory T Cell–independent Depletion of T Follicular Helper Cells

Article

Author: Ballesteros-Tato, André ; León, Beatriz ; Papillion, Amber ; Foote, Jeremy B. ; Bachus, Holly ; De Miguel, Carmen ; Santana, Silvia

AbstractThe expansion of T follicular helper (Tfh) cells correlates with disease progression in human and murine systemic lupus erythematosus (SLE). Unfortunately, there are no therapies to deplete Tfh cells. Importantly, low-dose rIL-2–based immunotherapy shows potent immunosuppressive effects in SLE patients and lupus-prone mice, primarily attributed to the expansion of regulatory T cells (Tregs). However, IL-2 can also inhibit Tfh cell differentiation. In this study, we investigate the potential of low-dose rIL-2 to deplete Tfh cells and prevent autoantibody responses in SLE. Our data demonstrate that low-dose rIL-2 efficiently depletes autoreactive Tfh cells and prevents autoantibody responses in lupus-prone mice. Importantly, this immunosuppressive effect was independent of the presence of Tregs. The therapeutic potential of eliminating Tfh cells was confirmed by selectively deleting Tfh cells in lupus-prone mice. Our findings demonstrate the critical role of Tfh cells in promoting autoantibody responses and unveil, (to our knowledge), a novel Treg-independent immunosuppressive function of IL-2 in SLE.

01 Sep 2024·Protein Expression and Purification

Soluble expression of recombinant human interleukin-2 in Escherichia coli and its facile production

Article

Author: Yu, Rong ; Huang, Jingbei ; Zhang, Minhui ; Zhang, Chun ; Zheng, Yongxiang ; Wang, Pengyu ; Wang, Sa ; Song, Xiaotong

Recombinant human interleukin-2 (rhIL-2) represents one of the most difficult-to-produce cytokines in E. coli due to its extreme hydrophobicity and high tendency to formation of inclusion bodies. Refolding of rhIL-2 inclusion bodies always represents cumbersome downstream processes and low production efficiency. Herein, we disclosed a fusion strategy for efficiently soluble expression and facile production of rhIL-2 in E. coli Origami B (DE3) host. A two-tandem SUMO fusion partner (His-2SUMO) with a unique SUMO protease cleavage site at C-terminus was devised to fuse with the N-terminus of rhIL-2 and the fusion protein (His-2SUMO-rhIL-2) was almost completely expressed in a soluble from. The fusion partner could be efficiently removed by Ulp1 cleavage and the rhIL-2 was simply produced by a two-step Ni-NTA affinity chromatography with a considerable purity and whole recovery. The eventually obtained rhIL-2 was well-characterized and the results showed that the purified rhIL-2 exhibits a compact and ordered structure. Although the finally obtained rhIL-2 exists in a soluble aggregates form and the aggregation probably has been occurred during expression stage, the soluble rhIL-2 aggregates remain exhibit comparable bioactivity with the commercially available rhIL-2 drug formulation.

News (Medical) associated with Aldesleukin

14 Nov 2024

·www.prnewswire.com

Biotech Companies' Q3 Updates: Promising Cancer Treatments on the Horizon

USA News Group News Commentary Issued on behalf of Oncolytics Biotech Inc. VANCOUVER, BC, Nov. 14, 2024 /PRNewswire/ -- USA News Group News Commentary – As many biotech companies within the oncology space begin to roll out their end-of-quarter results, the American Medical Association is pointing out the alarming trend of rising cancer rates, especially with younger people. According to data released from the National Cancer Institute (NCI), a division of the National Institutes of Health (NIH), a map shared by Newsweek showed that the prevalence of cancer varies significantly from state to state. Thankfully, there are plenty of new breakthroughs in the fight against cancer that the World Economic Forum recently highlighted, which are giving hope. Behind the scenes, biotech companies are making strides, with several touting their recent wins in their Q3 2024 financial results, including developments from O ncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), ImmunityBio, Inc. (NASDAQ: IBRX), Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), Syndax Pharmaceuticals, Inc. (NASDAQ: SNDX), and SpringWorks Therapeutics, Inc. (NASDAQ: SWTX). The article continued: As reported by The Guardian, a new study is raising hopes of treating aggressive cancers by zapping rogue DNA that helps tumors thrive and become resistant to chemotherapy. Showing the shifting market, researchers at Statista recently released a report showing the Top 5 Oncology Products Worldwide by Market Share in 2017 and 2024. Oncolytics Biotech® Reports Third Quarter 2024 Financial Results and Operational Highlights Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, recently reported their Q3 2024 financial results and operational highlights. Among these highlights included impressive overall survival benefit results from BRACELET-1 data in HR+/HER2- metastatic breast cancer affirming its pelareorep + paclitaxel combination should be evaluated in a registrational study. "With positive BRACELET-1 results, we have two randomized phase two studies confirming pelareorep's potential in HR+/HER2- metastatic breast cancer," said Wayne Pisano, Chair of Oncolytics' Board of Directors and Interim CEO of Oncolytics. "After discussions with regulators and key opinion leaders and based on an estimated overall survival benefit of more than a year provided by pelareorep-based therapy, a registration-enabling study that is designed to support an accelerated approval is the next logical step for the development of pelareorep." In the BRACELET-1 study, pelareorep combined with paclitaxel significantly improved outcomes for patients with advanced HR+/HER2- breast cancer. Patients receiving this treatment lived without cancer progression for an average of 12.1 months, compared to just 6.4 months with paclitaxel alone—showing a benefit of nearly six months. Additionally, 64% of patients treated with pelareorep and paclitaxel lived for at least two years, compared to only 33% for paclitaxel alone. Median overall survival could not be calculated because over half of the patients on pelareorep were still alive at the study's end, but if they only lived to their next follow-up, their survival would average 32.1 months, notably higher than the 18.2 months for paclitaxel alone. Oncolytics also highlighted upcoming milestones in its GOBLET study to include efficacy data from the anal cancer cohort and safety run-in data from the modified FOLFIRINOX pancreatic cancer cohort. "We continue to develop our gastrointestinal cancer program and look forward to presenting updated efficacy data from our anal cancer cohort and safety data from our new modified FOLFIRNOX pancreatic cancer cohort," continued Pisano. "Both of these indications represent a significant unmet medical need, and we have shown pelareorep provides the potential to meaningfully improve patient outcomes. This coming year will be critical for pelareorep, as well as for Oncolytics, and I've never been more confident in the potential pelareorep can deliver to cancer patients in need." Also, as of September 30, 2024, Oncolytics had a cash position of $19.6 million, providing a cash runway through key milestones and into 2025. Looking ahead, in H1 2025, Oncolytics is set to finalize the master protocol for the adaptive registration-enabling trial for pelareorep, gemcitabine, nab-paclitaxel, and atezolizumab in first-line pancreatic ductal adenocarcinoma (PDAC) with the Global Coalition for Adaptive Research (GCAR) and submit it to the FDA. Oncolytics also expects in H1 2025: safety run-in data from cohort 5 of the GOBLET study, investigating pelareorep and modified FOLFIRNOX (mFOLFIRINOX) with or without atezolizumab in newly diagnosed pancreatic cancer; and updated efficacy data from cohort 4 of the GOBLET study, investigating pelareorep and atezolizumab in second-line or later anal cancer. As well, mid 2025 should see the first patient enrolled in registration-enabling study evaluating pelareorep and paclitaxel in metastatic HR+/HER2- breast cancer, and H2 2025 should see initial efficacy results from cohort 5 of the GOBLET study, investigating pelareorep and mFOLFIRINOX with or without atezolizumab in newly diagnosed pancreatic cancer. CONTINUED… Read this and more news for Oncolytics Biotech at: In other industry developments and happenings in the market this week include: ImmunityBio, Inc. (NASDAQ: IBRX), an immunotherapy innovator, recently reported its Q3 2024 financial results, which included highlights such as its ANKTIVA® receiving a J-code (HCPCS Level II Code) effective January 1, 2025, and becoming widely accessible to patients through commercial and government insurance programs (VA, DoD, Medicare), leading ImmunityBio to secure coverage for over 200 million medical lives through medical reimbursement policies. "The U.S. launch of ANKTIVA for [non-muscle invasive bladder cancer with carcinoma in situ] (NMIBC CIS) continues to gain momentum, and we are pleased to see the clinical impact for patients," said Richard Adcock, President and CEO of ImmunityBio. "Our permanent J-code has been issued by Centers for Medicare and Medicaid Services and will be effective January 1, 2025. Our submission of ANKTIVA for NMIBC CIS to the MHRA in the UK for potential approval demonstrates our plans for global expansion. Further, we anticipate an EU submission this quarter." The financial results came just weeks after ImmunityBio announced that the first patients had been dosed in an initial trial studying the potential of the company's CAR-NK cell therapy targeting CD-19 in the treatment of non-Hodgkin's lymphoma (NHL). Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a commercial biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, recently reported its Q3 2024 financial results and corporate updates. Among the highlights were the reporting that significant demand for Amtagvi™ (Lifileucel) continues with $58.6M in Total 3Q24 Product Revenue and Iovance reaffirming guidance of $160-$165 million for FY 2024 and $450-$475 million for FY 2025 of total product revenue. " Iovance is executing a successful U.S. commercial launch of Amtagvi™ for patients with previously treated advanced melanoma," said Frederick Vogt, Ph.D., J.D., Interim President and CEO of Iovance. "Robust demand for Amtagvi and Proleukin® continues to grow as our expanding network of authorized treatment centers (ATCs) and outreach to community oncologists broaden the utilization of Amtagvi, driving a higher volume of patient referrals. Demand trends are expected to accelerate growth throughout the remainder of the year and over the following years. As a fully integrated company, Iovance is well positioned to remain the global leader in innovating, developing, and delivering current and future generations of TIL cell therapy for patients with cancer." Syndax Pharmaceuticals, Inc. (NASDAQ: SNDX), a commercial-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, recently reported its Q3 2024 financial results and business update. Within the highlights were the mention that new revumenib and Niktimvo™ clinical data will be highlighted at the 66th ASH Annual Meeting and that mNPM1 AML topline data from AUGMENT-101 is expected in Q4 2024, with a potential sNDA filing in H1 2025. "This has been a historic period for Syndax as we transitioned to a commercial-stage company with the approval of Niktimvo," said Michael A. Metzger, CEO of Syndax. "We have a very exciting quarter ahead with the anticipated FDA approval and U.S. launch of revumenib for adults and pediatrics with R/R KMT2Ar acute leukemia, as well as the expected readout of topline pivotal data from patients with R/R mNPM1 AML. Our commercial organization is well-prepared to launch revumenib and leverage our first-to-market position to drive long-term value creation." SpringWorks Therapeutics, Inc. (NASDAQ: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, recently reported their Q3 2024 financial results and provided an update on recent company developments that included achieving $49.3 million in OGSIVEO® (nirogacestat) net product revenue in the quarter, and being granted FDA Priority Review on NDA and received validation of EU Marketing Authorization Application for mirdametinib for the treatment of adults and children with NF1-PN. "As we approach nearly one full year on market, we are very encouraged by the metrics we are seeing regarding the breadth of physician prescribing, the number of patients on OGSIVEO, and the number of patients identified who may stand to benefit in the future from our medicine," said Saqib Islam, CEO of SpringWorks. "Our focus for the remainder of the year is to continue building on OGSIVEO's momentum in the U.S. while working to also bring it to patients in Europe, to advance our commercial preparations for mirdametinib in anticipation of serving patients with NF1-PN in the U.S. and Europe, and to progress our emerging portfolio." Source: CONTACT: USA NEWS GROUP [email protected] (604) 265-2873 DISCLAIMER: Nothing in this publication should be considered as personalized financial advice. We are not licensed under securities laws to address your particular financial situation. No communication by our employees to you should be deemed as personalized financial advice. Please consult a licensed financial advisor before making any investment decision. This is a paid advertisement and is neither an offer nor recommendation to buy or sell any security. We hold no investment licenses and are thus neither licensed nor qualified to provide investment advice. The content in this report or email is not provided to any individual with a view toward their individual circumstances. USA News Group is a wholly-owned subsidiary of Market IQ Media Group, Inc. ("MIQ"). MIQ has been paid a fee for Oncolytics Biotech Inc. advertising and digital media from the company directly. There may be 3rd parties who may have shares of Oncolytics Biotech Inc., and may liquidate their shares which could have a negative effect on the price of the stock. This compensation constitutes a conflict of interest as to our ability to remain objective in our communication regarding the profiled company. Because of this conflict, individuals are strongly encouraged to not use this publication as the basis for any investment decision. The owner/operator of MIQ own shares of Oncolytics Biotech Inc. which were purchased in the open market, and reserve the right to buy and sell, and will buy and sell shares of Oncolytics Biotech Inc. at any time without any further notice commencing immediately and ongoing. We also expect further compensation as an ongoing digital media effort to increase visibility for the company, no further notice will be given, but let this disclaimer serve as notice that all material, including this article, which is disseminated by MIQ has been approved by Oncolytics Biotech Inc.; this is a paid advertisement, we currently own shares of Oncolytics Biotech Inc. and will buy and sell shares of the company in the open market, or through private placements, and/or other investment vehicles. While all information is believed to be reliable, it is not guaranteed by us to be accurate. Individuals should assume that all information contained in our newsletter is not trustworthy unless verified by their own independent research. Also, because events and circumstances frequently do not occur as expected, there will likely be differences between the any predictions and actual results. Always consult a licensed investment professional before making any investment decision. Be extremely careful, investing in securities carries a high degree of risk; you may likely lose some or all of the investment. SOURCE USA News Group WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

ImmunotherapyFinancial Statement

13 Nov 2024

·www.globenewswire.com

Medicenna Announces Upcoming Presentations at the 29th Annual Meeting of the Society for Neuro-Oncology (SNO) and the 2024 San Antonio Breast Cancer Symposium (SABCS)

TORONTO and HOUSTON, Nov. 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 today that it will present pre-clinical data on MDNA11 and IL-2 Superkines in glioblastoma models at the 29th Annual Meeting of the Society of Neuro-Oncology (SNO) taking place in Houston, Texas from November 21 – 24, 2024. The Company will also present pre-clinical data in aggressive metastatic models of breast cancer incorporating MDNA11 pre-treatment prior to surgery (“neoadjuvant”) at the 2024 San Antonio Breast Cancer Symposium (SABCS), the world’s largest breast cancer conference taking place in San Antonio, Texas from December 10 – 13, 2024. Details for the poster presentations are as follows: 29th Annual SNO Meeting: Title: Invigorating effector immune cells with highly selective IL-2R agonists and potential synergy with tumor targeting therapeutics for treatment of glioblastomas Session Date: Friday, November 22, 2024Session Time: 7:30 – 9:30 PM CTAbstract Number: IMMU-62 2024 SABCS: Title: Neo-adjuvant administration of MDNA11, a long-acting IL-2 Superkine, prevents metastasis, protects against tumor rechallenges and provides long-term survival in an orthotopic model of breast cancer Session Date: Thursday, December 12, 2024Session Time: 12:00 – 2:00 PM CTAbstract: SESS-1335 Following the conclusion of the Annual SNO Meeting and the SABCS, copies of the posters will be available 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 a monotherapy and in combination with pembrolizumab (KEYTRUDA®). 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. 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. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. 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 potential and safety profile of MDNA11 and IL-2 super-agonists as well as MDNA11’s and IL-2 super-agonists’ ultimate treatment potential. 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/Media Contact: Christina CameronInvestor Relations, Medicenna Therapeutics(647) 953-0673ir@medicenna.com

ImmunotherapyOrphan DrugPhase 2ASCO

11 Nov 2024

·www.globenewswire.com

Medicenna Announces Positive Single-Agent Activity of MDNA11 from Dose Expansion Cohort and Encouraging Safety Profile in Combination with KEYTRUDA® (pembrolizumab) at the 39th Annual Meeting of SITC

Single-agent MDNA11 shows a 30% objective response rate (3 of 10) in the monotherapy dose expansion cohort among patients with advanced and/or metastatic solid tumors who had disease progression with immune checkpoint inhibitor (ICI) therapy Among ICI-resistant, high-dose MDNA11, phase 2-eligible patients in the monotherapy escalation and expansion cohorts (N=20), the response rate is 25% (5/20) including 1 complete response (CR) and 4 partial responses (PR) Treatment responses have been observed in 2 of 3 microsatellite instability-high (MSI-H) patients, both with pancreatic cancer, and in 3 of 11 patients with cutaneous melanoma including one CR With no dose limiting toxicities (DLTs) or new safety signals observed in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) to date, the combination dose escalation is enrolling patients at the highest dose of MDNA11 evaluated in monotherapy (120 µg/kg) Among 5 efficacy-evaluable patients in the combination dose escalation arm, tumor control (PR or SD) was observed in 4 patients including a PR in a microsatellite-stable (MSS) colon cancer patient TORONTO and HOUSTON, Nov. 11, 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, presented updated clinical results from the ongoing monotherapy dose expansion and combination dose escalation portions of the Phase 1/2 ABILITY-1 (A Beta-only IL-2 ImmunoTherapY) study evaluating MDNA11, a long-acting ‘beta-enhanced not-alpha’ interleukin-2 (IL-2) super-agonist, as monotherapy or in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with advanced solid tumors, at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), held in Houston, Texas, on November 9th, 2024. “We are thrilled to share promising results from the Phase 1/2 ABILITY-1 study, with MDNA11 continuing to show deep and durable single-agent activity in patients resistant to checkpoint therapy including 2 patients with metastatic, treatment-refractory pancreatic cancer,” said Fahar Merchant, Ph.D., President and CEO of Medicenna. “We are especially pleased to see that MDNA11 in combination with KEYTRUDA® is demonstrating a favorable safety profile, robust pharmacodynamics and early signs of anti-tumor activity in heavily pre-treated patients allowing us to bolster the dose of MDNA11 to 120 µg/kg every 2 weeks and begin to evaluate dosing at a more convenient frequency of once every three weeks. We look forward to sharing additional clinical updates from the monotherapy and combination arms at medical conferences in the first half of 2025.” Key findings from the on-going monotherapy and combination dose escalation portions of the ABILITY-1 study at the time of data cut-off (i.e. October 15th, 2024) include: Monotherapy Tumor Response in Checkpoint 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 irrespective of tumor origin.The ORR is 25% (1 CR, 4 PR) 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.Objective responses included: 2 PRs among 3 MSI-H patients (ORR of 66.7%) with both responders having pancreatic ductal adenocarcinoma (PDAC). One patient with MSI-H PDAC was initially misclassified as MSI-H small bowel cancer with metastases in the pancreas.1 CR and 2 PRs among 11 patients with cutaneous melanoma (ORR of 27.3%).SD in 6 patients including 3 with duration > 24 weeks, yielding a clinical benefit rate of 40% (8/20). Monotherapy Safety Profile Key findings from the monotherapy dose escalation and ongoing monotherapy expansion arms of the ABILITY-1 study demonstrate MDNA11’s favorable safety profile: As previously reported, DLT or vascular leak syndrome were not observed during monotherapy dose escalation with a majority (94%) of treatment-related adverse events (TRAEs) being either grade 1 or 2 and resolving within 48 hours; grade 3 TRAEs mainly constituted asymptomatic transient LFT elevations; one isolated grade 4 TRAE was observed with asymptomatic transient LFT elevation in the monotherapy dose expansion arm which resolved within 72 hours without intervention. Repeat administration of MDNA11 at the target doses continues to improve tolerability. Monotherapy Pharmacodynamics Pharmacodynamic analyses showed potent and durable systemic immune responses following MDNA11 administration with clear evidence of immune activation in the tumor microenvironment: MDNA11 showed significant increases in markers of stemness, central and effector memory and enhanced effector function in circulating CD8+ T and NK cells.Analysis of paired biopsies showed increased tumor infiltration of CD25+ activated CD8+ T cells and NK cells post-MDNA11 treatment. Combination Dose Escalation Safety Profile No DLTs, grade 4 or 5 TRAEs were observed in combination dose escalation cohorts 1 or 2 (60 µg/kg Q2W or 90 µg/kg Q2W MDNA11 with 400 mg Q6W KEYTRUDA®) during the DLT observation period. The Safety Review Committee approved enrollment of the next higher-dose cohorts as follows: Cohort 3: 120 µg/kg Q2W MDNA11 and 400 mg Q6W KEYTRUDA®Cohort 4: 120 µg/kg Q3W MDNA11 and 400 mg Q6W KEYTRUDA® Combination Dose Escalation Pharmacodynamics Early pharmacodynamic analyses demonstrated robust lymphocyte expansion which was sustained with repeat dosing at both 60 µg/kg and 90 µg/kg Q2W MDNA11 in combination with 400 mg Q6W KEYTRUDA®. Combination Dose Escalation Tumor Response Encouraging preliminary signs of anti-tumor activity were observed with MDNA11 in combination with KEYTRUDA® (400 mg Q6W) in dose escalation cohorts 1 (60 µg/kg Q2W MDNA11) and 2 (90 µg/kg Q2W MDNA11). Among 5 heavily pre-treated efficacy-evaluable patients, tumor control (PR or SD) was observed in 4 patients including a PR in a microsatellite-stable (MSS) colon cancer patient. A copy of the poster and a related slide deck have 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 6-12 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 a combination dose expansion cohort. 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. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Forward-Looking Statements This news release contains 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 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. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated 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. 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/Media Contact: Christina CameronInvestor Relations, Medicenna Therapeutics(647) 953-0673ir@medicenna.com

Clinical ResultImmunotherapyPhase 2Orphan DrugASCO

100 Deals associated with Aldesleukin

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KEGG	Wiki	ATC	Drug Bank
D00748	-	L03AC01	DB00041

R&D Status

Approved

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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
Malignant melanoma, metastatic	Phase 3	US	National Cancer Institute	13 Nov 1997
Melanoma, Cutaneous Malignant	Phase 3	US	National Cancer Institute	13 Nov 1997
Metastatic melanoma	Phase 3	US	National Cancer Institute	13 Nov 1997
Burkitt Lymphoma	Discovery	US	National Cancer Institute	01 May 1995
Diffuse Large B-Cell Lymphoma	Discovery	US	National Cancer Institute	01 May 1995
Immunoblastic Large-Cell Lymphoma	Discovery	US	National Cancer Institute	01 May 1995
Recurrent Grade 3a Follicular Lymphoma	Discovery	US	National Cancer Institute	01 May 1995
Recurrent Non-Hodgkin Lymphoma	Discovery	US	National Cancer Institute	01 May 1995
Stage II Non-Contiguous Adult Diffuse Small Cleaved Cell Lymphoma	Discovery	US	National Cancer Institute	01 May 1995
Metastatic Renal Cell Carcinoma	Discovery	US	National Cancer Institute	01 Apr 1991

Clinical Result

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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)	pwzbrxudcg(lvrhdoieef) = xidnsmdlvs iphuisxgaq (qqfrtzzngm, bsmynlxjty - gltlvtkgip) View more	-	07 Nov 2024
				Cyclophosphamide+IL-2 (Dose Level 2)	pwzbrxudcg(lvrhdoieef) = phkfrwqzbr iphuisxgaq (qqfrtzzngm, ztsmkgsysx - jjyuujymol) View more
NCT05267626 (SITC2024) Manual	Phase 1/2	Advanced Malignant Solid Neoplasm	-	AU-007	(vafudiitzu) = None wlqtwgqdnr (uxqebrwixz ) View more	Positive	05 Nov 2024
				AU-007 + aldesleukin
EUCTR2017-002323-25-DK \| NCT03296137 (CTgov)	Phase 1/2	Neoplasms	25	infiltrating lymphocytes+ipilimumab+Fludara+Cyclophosphamide+proleukin (All Participants)	(tgatvpvfug) = ghinguxtaf llhuoygpvy (nkwiwpcerv, ujjxcutozh - ieqgebroaq) View more	-	26 Oct 2024
				infiltrating lymphocytes+ipilimumab+Fludara+Cyclophosphamide+proleukin (Treated Participants)	(kffmlqfcrt) = qiwqfkdbil wenpojvfhl (fvbcgruswl, gtvsjfpsgs - teatnpatnr) View more
NCT01740557 (CTgov)	Phase 1/2	Metastatic melanoma	10	Quality-of-Life Assessment+CXCR2-transduced Autologous Tumor Infiltrating Lymphocytes+Fludarabine Phosphate+Cyclophosphamide+NGFR-transduced Autologous T Lymphocytes+Aldesleukin	sbwfoyjpoz(choynqddyt) = iwiictpxxg blohkftzwo (pcberzoqkk, uyvislosgq - xlgmrbrrsa) View more	-	08 Oct 2024
NCT02027935 (CTgov)	Phase 2	Metastatic melanoma	16	Autologous CD8+ Melanoma Specific T Cells+ipilimumab+Cyclophosphamide+Aldesleukin	gtsegadyeq(flgwwxuwsd) = cshyyllmou iiuiztwadn (rvbdmqidoo, elxoarvysw - raxeyrjxgg) View more	-	08 Oct 2024
NCT03233828 (IL-2, CTgov)	Phase 3	Melanoma, Cutaneous Malignant \| Visible Lesion	1	Aldesleukin (Intralesional IL-2 Injection)	ihpcfizywj(bwxiqwsjwb) = dmkycexewc hjvkvhgjlk (hpckkzcern, rsxtwseukb - nbvufdkwyj) View more	-	24 Jul 2024
				Saline (Saline Injection)	ihpcfizywj(bwxiqwsjwb) = vbwgiepljf hjvkvhgjlk (hpckkzcern, scnijliwjc - lsmyivvhdb) View more
NCT05267626 (ASCO2024) Manual	Phase 1/2	Advanced Malignant Solid Neoplasm	53	AU-007 Q2W (Arm 1A)	(jsfovmepky) = lbpidjbcja kgmlovdoap (stmjnxnyss )	Positive	24 May 2024
				AU-007 Q2W + one aldesleukin (Arm 1B)	(jsfovmepky) = tigqmrlvzz kgmlovdoap (stmjnxnyss ) View more
NCT01856023 (PROCLIVITY02, CTgov)	Phase 4	Metastatic melanoma	29	ipilimumab+High Dose Interleukin-2 (Treatment Arm 1)	eghwbxxhmx(srzwvfjkls) = wwfcstwhff wdigpjepqp (clvpzdjtzb, bldxdnlxwf - lguxdgiauf)	-	05 Dec 2023
				ipilimumab+High Dose Interleukin-2 (Treatment Arm 2)	eghwbxxhmx(srzwvfjkls) = qggojzfvmi wdigpjepqp (clvpzdjtzb, ozjdvzgsem - ptpfwcjrhc)
NCT05267626 (Phase 1 study, SITC2023)	Phase 1	Advanced Malignant Solid Neoplasm	24	AU-007	gthigcrvfw(qdjxpbrjiu) = no DLTs gbrqfgybmg (zftqvkpfyo ) View more	Positive	02 Nov 2023
				AU-007 + aldesleukin
NCT02774291 (CTgov)	Early Phase 1	Brain metastases	3	Laboratory Biomarker Analysis+Fludarabine Phosphate+Cyclophosphamide+Filgrastim+Aldesleukin+Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes	eoibfkopbl(grdfaexzcg) = nhxuckjtvx nyxieknovh (fvrtzycfhn, iunhfzvskt - taghjtbuef) View more	-	04 Aug 2023

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