A Phase 1 Dose Escalation Study of BMS-982470 (Recombinant Interleukin-21, rIL-21) in Combination With BMS-936558 (Anti-PD-1) in Subjects With Advanced or Metastatic Solid Tumors

The purpose of this study is to determine whether the combination of the 2 drugs being investigated (IL-21 and anti-PD-1) is safe, and provide preliminary information on the clinical benefits of two different schedules of the combination.

Start Date01 Jun 2012

Sponsor / Collaborator

Bristol Myers Squibb Co.

NCT01489059

/ CompletedPhase 1

A Phase I Dose Escalation Study of BMS-982470 (Recombinant Interleukin 21, rIL-21) in Combination With Ipilimumab in Subjects With Unresectable Stage III or Stage IV Melanoma

The purpose of this study is to determine whether the combination of interleukin-21 (IL-21) and Ipilimumab in subjects with melanoma is safe, and provide preliminary information on the clinical benefits of the combination compared with Ipilimumab alone

Start Date01 Dec 2011

Sponsor / Collaborator

Bristol Myers Squibb Co.

NCT01152788

/ CompletedPhase 2IIT

A Randomized Phase II Study of Interleukin-21 (rIL-21) Versus Dacarbazine (DTIC) in Patients With Metastatic or Recurrent Melanoma

The purpose of this study is to find out what effects an experimental drug, called interleukin 21 or rIL-21, will have on malignant melanoma and whether these effects look promising compared to dacarbazine. In addition, this study will look at the side effects of rIL-21, and some special blood tests will be done to check the level of rIL-21 in the blood. This study will also look at previously removed melanoma tissue to determine which patients might benefit most from this treatment.
This research is being done because currently there is no effective treatment for this type of cancer.

Start Date05 Aug 2010

Sponsor / Collaborator

NCIC Clinical Trials Group

100 Clinical Results associated with Denenicokin

100 Translational Medicine associated with Denenicokin

100 Patents (Medical) associated with Denenicokin

325

Literatures (Medical) associated with Denenicokin

01 May 2025·INTERNATIONAL IMMUNOPHARMACOLOGY

Attenuated Salmonella carrying IL-21 overexpression plasmid enhances radiotherapy efficacy in a preclinical model of melanoma

Article

Author: Yin, Zhinan ; Geng, Jiaxin ; Cai, Jingjing ; Yang, Zishan ; Wei, Yuqing ; Chen, Caili ; Ren, Feng ; Wei, Tian ; Jiang, Hanyu ; Jia, Huijie ; Chen, Zhihan ; Chu, Zhili ; Lei, Mengyu ; Zhang, Yongxi ; Zhao, Tiesuo ; Peng, Qi

Melanoma, known for its aggressive behavior and tendency to metastasize to the brain and lungs, is a formidable challenge in oncology. Radiotherapy is a potent treatment for localized solid tumors, effective against both intracranial and extracranial metastases. Yet, some melanoma patients exhibit substantial resistance to radiotherapy, with the underlying mechanisms of this resistance remaining elusive. While radiotherapy can stimulate the infiltration of immune cells, thereby triggering a range of immunostimulatory effects, it can also suppress the tumor microenvironment (TME), limiting its effectiveness. In physiological conditions, cytokines inhibit the activity of immunosuppressive cells through paracrine and autocrine signaling, while also activating immune cells to boost antitumor responses. Here, we found that Interleukin (IL)-21 expression was higher in the mice with good radiotherapy response to melanoma than in the mice with poor radiotherapy response. Interestingly, we also observed the higher infiltration of M2 TAMs and lower CD8⁺ T cells in the group with poor radiotherapy response. To tackle this issue, we explored the therapeutic potential of a plasmid encoding IL-21, delivered via attenuated Salmonella, in mice bearing melanomas. Our findings revealed that IL-21 administration significantly reduced M2 TAMs infiltration and enhanced CD8⁺ T cells infiltration and granzyme B (GZMB) expression within melanoma tumors. Most importantly, the combination of IL-21 with radiotherapy led to markedly tumor reduction compared to either treatment alone. This research highlights the potential of IL-21 as a valuable adjunct to radiotherapy in the treatment of melanoma, presenting a promising strategy for enhancing antitumor immune responses and optimizing patient outcomes.

01 May 2025·MICROBIAL PATHOGENESIS

Characteristics and functions of interleukin 21 in channel catfish (Ictalurus punctatus)

Article

Author: Wang, Hui ; Yang, Yibin ; Yang, Qiuhong ; Huang, Yucong ; He, Hao ; Zhu, Xia ; Ai, Xiaohui ; Deng, Ping ; Dong, Jing

Interleukin-21 (IL-21) is mainly produced by CD4⁺ T cells and NKT cells, belonging to the gamma chain (γc) family. It promotes the proliferation, activation, and differentiation of immune cells and activates the JAK-STAT, MAPK signaling, and PI3K pathways to regulate immune responses, crucially impacting anti-infectious inflammatory responses. In this study, IL-21 was successfully identified in channel catfish (Ictalurus punctatus, Ip), with a coding sequence (CDS) length of 438 bp encoding a 145-amino acid (aa) protein. The signal peptide comprised 19 aa, while the mature peptide consists of 126 aa, featuring four α-helix structures and two pairs of disulfide bonds from four conserved cysteine residues. qPCR data revealed highest IpIL-21 expression in channel catfish gills and spleen. Bacterial and viral infections upregulated IpIL-21 expression across multiple tissues. Poly(I:C) specifically enhanced IpIL-21 expression in channel catfish kidney cells (CCK) at 48 h post-infection (hpi). In vitro, recombinant IpIL-21 (rIpIL-21) protein induced upregulation of IL-10, IL-21, IL-1β, and STAT3 expression in CCK, while inhibiting IL-22 and IL-26 expression. IL-6 and IL-20 expressions were inhibited at low doses and induced at high doses, demonstrating a dose-dependent pattern. These findings underscored IpIL-21's significance as a critical immune factor in channel catfish, pivotal for the antibacterial inflammatory response defense system.

17 Apr 2025·BLOOD

HSP-CAR30 with a high proportion of less-differentiated T cells promotes durable responses in refractory CD30+ lymphoma

Article

Author: Caballero, Ana Carolina ; Sierra, Jorge ; Soria, José Manuel ; Garcia-Cadenas, Irene ; Ujaldón-Miró, Cristina ; Riba, Mireia ; Briones, Javier ; Pujol-Fernández, Paula ; Escudero-López, Eva ; Iranzo, Eva ; Moreno-Martinez, Maria-Estela ; Alvarez-Fernández, Carmen ; Martino, Rodrigo ; Montserrat-Torres, Rosanna ; Jara-Bustamante, Paola ; Escribà-Garcia, Laura ; Ezquerra, Pol ; Esquirol, Albert ; Guardiola-Perello, Maria

Abstract:

CD30-directed chimeric antigen receptor T-cell therapy (CART30) has limited efficacy in relapsed or refractory patients with CD30+ lymphoma, with a low proportion of durable responses. We have developed an academic CART30 cell product (HSP-CAR30) by combining strategies to improve performance. HSP-CAR30 targets a proximal epitope within the nonsoluble part of CD30, and the manufacturing process includes a modulation of ex vivo T-cell activation, as well as the addition of interleukin-21 (IL-21) to IL-7 and IL-15 to promote stemness of T cells. We translated HSP-CAR30 to a phase 1 clinical trial of 10 patients with relapsed/refractory classic Hodgkin lymphoma (HL) or CD30+ T-cell non-Hodgkin lymphoma. HSP-CAR30 was mainly composed of memory stem–like (TSCM-like) and central memory (TCM) CAR30+ T cells (87.5% ± 5%). No dose-limiting toxicities were detected. Six patients had grade 1 cytokine release syndrome, and no patient developed neurotoxicity. The overall response rate was 100%, and 5 of 8 patients with HL achieved complete remission (CR). An additional patient with HL achieved CR after a second HSP-CAR30 infusion. Remarkably, 60% of patients have ongoing CR after a mean follow-up of 34 months. CAR30+ T cells at expansion peak had a predominance of TSCM and TCM cells, and CAR30+ T cells remained detectable in 3 of 5 evaluable patients at least 12 months after infusion. Our study shows that selection of the epitope targeting CD30 and ex vivo preservation of less-differentiated memory T cells may enhance the efficacy of CART30 in patients with refractory HL. This trial is registered at www.clinicaltrials.gov (NCT04653649).

News (Medical) associated with Denenicokin

08 May 2025

·www.globenewswire.com

Werewolf Therapeutics Reports First Quarter 2025 Financial Results and Provides Business Update

– WTX-124 Phase 1/1b clinical trial on track for data readouts and interactions with the FDA in the second half of the year – – First patient dosed in the Phase 1b/2 clinical trial of WTX-330, seeking to build on the clinical activity and tolerability demonstrated in the recently completed WTX-330 first-in-human Phase 1 trial – – Company announces development of its proprietary INDUCER™ T cell engager molecules; development candidate targeted by the end of the second quarter of 2025 – – Updated cash guidance provides runway into the fourth quarter of 2026 – WATERTOWN, Mass., May 08, 2025 (GLOBE NEWSWIRE) -- Werewolf Therapeutics, Inc. (the “Company” or “Werewolf”) (Nasdaq: HOWL), an innovative biopharmaceutical company pioneering the development of conditionally activated therapeutics engineered to stimulate the body’s immune system for the treatment of cancer and other immune-mediated conditions, today provided a business update and reported financial results for the first quarter ended March 31, 2025. “Werewolf continues to build on our promising data and progress across our clinical-stage programs,” said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf. “We remain on track in our Phase 1/1b clinical trial evaluating WTX-124 to share interim data and meet with the FDA to discuss potential registrational pathways in the second half of this year. Additionally, in recognition of Skin Cancer Awareness month, Werewolf is launching an educational campaign in May to highlight the differentiation of Werewolf’s conditionally activated therapeutics and patient experiences to date in the WTX-124 clinical trial. I am also pleased to report that we recently initiated a Phase 1b/2 clinical trial of WTX-330 to explore antitumor activity and optimize the exposure of our IL-12 INDUKINE molecule in the tumor microenvironment. Finally, Werewolf has been making significant progress towards nominating its first INDUCER T cell engager development candidate in the second quarter of 2025, with preclinical data demonstrating that PREDATOR® masking technology successfully silenced peripheral activity and prevented cytokine release. We believe that our proprietary PREDATOR masking and targeting technology distinctly positions us to build a robust pipeline of T cell engagers with potentially best-in-class potency and safety profiles, filling a gap in the current immuno-oncology landscape.” Recent Highlights and Upcoming Milestones WTX-124: a systemically delivered, conditionally activated Interleukin-2 (IL-2) INDUKINE molecule being developed as monotherapy and in combination with pembrolizumab in multiple solid tumor types. All expansion arms are actively enrolling patients in the ongoing Phase 1/1b clinical trial at a recommended dose of 18 mg administered intravenously every two weeks (IV Q2W).During the second half of 2025, Werewolf plans to present interim data from the monotherapy and combination expansion arms, including tolerability, response rate, and durability, and to engage with regulatory authorities to discuss potential registrational pathways for WTX-124, including strategies for accelerated approval.The data continue to demonstrate clinically meaningful anti-tumor activity with a tolerable safety profile in patients who have previously been treated with immune checkpoint inhibitors.Launching a skin cancer awareness campaign educating various stakeholders on WTX-124 patient outcomes to date and the innovative science underlying Werewolf’s IL-2 cytokine therapy. WTX-330: a systemically delivered, conditionally activated Interleukin-12 (IL-12) INDUKINE molecule being developed in advanced or metastatic solid tumors. Initiated patient dosing in a Phase 1b/2 clinical trial (WTX-330x2102) to optimize the exposure of WTX-330 in the tumor microenvironment, following the encouraging clinical activity and tolerability seen in the WTX-330x2101 first-in-human study. Preclinical Portfolio: Werewolf’s previously announced development candidates WTX-712, its Interleukin-21 (IL-21) INDUKINE molecule, and WTX-518, its binding protein resistant Interleukin-18 (IL-18) INDUKINE molecule, for the treatment of cancer, and WTX-921, a first-of-its-kind Interleukin-10 (IL-10) INDUKINE molecule for the treatment of inflammatory bowel disease (IBD) and potentially other inflammatory diseases, are available for partnering.Werewolf has extended its conditional activation technology to T cell engagers, utilizing a novel and highly effective anti-CD3 masking strategy for its INDUCER T cell engager molecules. Preclinical data demonstrate that the Company’s PREDATOR masking technology successfully silenced peripheral activity and prevented cytokine release in its INDUCER molecules. The Company’s first INDUCER development candidate is expected to be nominated in the second quarter of 2025. Financial Results for the First Quarter of 2025: Cash position: As of March 31, 2025, cash and cash equivalents were $92.0 million, compared to $111.0 million as of December 31, 2024. Based on updated forecasting, the Company now believes its existing cash and cash equivalents as of March 31, 2025, will be sufficient to fund operational expenses and capital expenditure requirements into the fourth quarter of 2026.Research and development expenses: Research and development expenses were $13.1 million for the first quarter of 2025, compared to $12.9 million for the same period in 2024.General and administrative expenses: General and administrative expenses were $4.9 million for the first quarter of 2025, compared to $5.0 million for the same period in 2024.Net loss: Net loss was $18.1 million for the first quarter of 2025, compared to $16.2 million for the same period in 2024. About Werewolf Therapeutics:Werewolf Therapeutics, Inc., is an innovative biopharmaceutical company pioneering the development of therapeutics engineered to stimulate the body’s immune system for the treatment of cancer and other immune-mediated conditions. The Company is leveraging its proprietary PREDATOR® platform to design conditionally activated molecules that stimulate both adaptive and innate immunity with the goal of addressing the limitations of conventional proinflammatory immune therapies. Werewolf’s INDUKINE molecules are intended to remain inactive in peripheral tissue yet activate selectively in the tumor microenvironment. The Company’s most advanced clinical stage product candidates, WTX-124 and WTX-330, are systemically delivered, conditionally activated Interleukin-2 (IL-2) and Interleukin-12 (IL-12) INDUKINE molecules, respectively, for the treatment of solid tumors. Werewolf is advancing WTX-124 in multiple tumor types as a single agent and in combination with an immune checkpoint inhibitor and WTX-330 in multiple tumor types or Non-Hodgkin Lymphoma as a single agent. To learn more visit www.werewolftx.com. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Werewolf’s strategy, future operations, prospects, plans, and objectives of management; the projection of the cash runway; the expected timeline for the preclinical and clinical development of product candidates and the availability of data from such preclinical and clinical development; the potential activity and efficacy of product candidates in preclinical studies and clinical trials; and the anticipated safety profile of product candidates constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “aim,” “anticipate,” “believe,” “contemplate,” “continue,” “could,” “design,” “designed to,” “engineered,” “estimate,” “expect,” “goal,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “potential,” “predict,” “project,” “promise,” “should,” “target,” “will,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The Company may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the development of product candidates, including the conduct of research activities, and the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; the timing of and the Company’s ability to submit and obtain regulatory approval for investigational new drug applications; whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials; whether preliminary or interim data from a clinical trial will be predictive of the future results of the trial and future clinical trials; the Company’s ability to manage cash resources and obtain additional cash resources to fund the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; as well as the risks and uncertainties identified in the “Risk Factors” section of the Company’s most recent Form 10-K filed with the Securities and Exchange Commission (SEC), and in subsequent filings the Company may make with the SEC. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date of this press release. The Company anticipates that subsequent events and developments will cause its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this press release. WEREWOLF®, the WEREWOLF logo, PREDATOR®, INDUKINE™, INDUCER™, and other Werewolf trademarks, service marks, graphics and logos are trade names, trademarks or registered trademarks of Werewolf Therapeutics, Inc., in the United States or other countries. All rights reserved. Werewolf Therapeutics, Inc.Condensed Consolidated Statements of Operations (unaudited)(amounts in thousands, except share and per share data) Three Months EndedMarch 31, 2025 2024 Revenue: Collaboration revenue$— $742 Operating expenses: Research and development 13,120 12,908 General and administrative 4,871 4,996 Total operating expenses 17,991 17,904 Operating loss (17,991) (17,162)Other income (98) 969 Net loss$(18,089) $(16,193) Net loss per common share, basic and diluted$(0.40) $(0.39)Weighted-average common shares outstanding, basic and diluted 44,827,159 41,607,279 Werewolf Therapeutics, Inc.Selected Condensed Consolidated Balance Sheet Data (unaudited)(amounts in thousands) March 31, 2025 December 31, 2024Cash and cash equivalents$92,042 $110,995Working capital$82,788 $97,886Total assets$107,236 $126,929Total notes payable, net of discount and issuance costs$26,585 $26,095Total stockholders’ equity$57,307 $73,390 Investor Contact:Dan FerryLifeSci Advisors617.430.7576daniel@lifesciadvisors.com Media Contact:Amanda SellersDeerfield Group 301.332.5574amanda.sellers@deerfieldgroup.com Company Contact:Tim TrostChief Financial OfficerWerewolf Therapeuticsttrost@werewolftx.com

Financial StatementPhase 1Immunotherapy

10 Nov 2022

·pipelinereview.com

Asher Bio Presents New Preclinical Data at SITC 2022 Further Supporting Advancement of AB248 and AB821 as Highly Differentiated Cis-targeted Cancer Immunotherapies

-- AB248 demonstrates non-clinical activity and safety profile suggesting its potential as a best-in-class IL-2 -- -- AB821 shows differentiated anti-tumor activity and enhanced bioavailability over wild type IL-21 -- -- On track to initiate Phase 1 trial of AB248 in 4Q 2022; Plan to file investigational new drug (IND) application for AB821 in 2H 2023 -- SOUTH SAN FRANCISCO, CA, USA I November 10, 2022 I Asher Biotherapeutics, Inc. (Asher Bio), a biotechnology company focused on developing therapies to precisely engage specific immune cells to fight cancer, chronic viral infection, and autoimmune disease, today announced new preclinical data for AB248, its CD8-targeted interleukin-2 (IL-2) immunotherapy, and for AB821, its CD8-targeted interleukin-21 (IL-21) immunotherapy. The data will be presented at the Society for Immunotherapy in Cancer (SITC) 37th Annual Meeting, being held in Boston, Massachusetts, on November 8-12, 2022. “We are pleased to share new data on AB821, which support its continued development for the treatment of solid tumors” Tweet this “We are very pleased to share new data for both AB248 and AB821 at SITC, showcasing the power of our platform to efficiently generate product candidates that demonstrate highly selective T cell engagement, as well as differentiated pharmacodynamics, anti-tumor activity and tolerability across a range of in vitro and in vivo models,” said Ivana Djuretic, Ph.D., Chief Scientific Officer and Co-Founder of Asher Bio. “These data provide further validation that our cis-targeting approach enables us to activate only the desired immune cell type, potentially overcoming the pleiotropic effects that limited the clinical potential of previous immunotherapies. We look forward to advancing both programs as we aim to deliver on the promise of IL-2 and IL-21 as high-value targets to improve the care and treatment of people living with cancer.” New Preclinical Data for AB248, Asher Bio’s CD8-Targeted IL-2 In a poster presentation entitled, “CD8+ T cell selectivity of AB248 is essential for optimal anti-tumor activity and safety in nonclinical models,” lead author Kelly Moynihan, Ph.D., Senior Director and Project Team Leader at Asher Bio, described new preclinical data further differentiating AB248 from “not-α” IL-2 therapies and elucidating the mechanisms by which AB248 achieves enhanced anti-tumor activity and greater tolerability. The data show: “We are particularly encouraged to report new preclinical findings that underscore AB248’s differentiation from broadly acting IL-2-based therapies,” said Dr. Moynihan. “In addition to reinforcing the importance of selectively activating only CD8+ T cells for potentially improved safety and tolerability, new analyses presented at SITC suggest that AB248 may profoundly impact the tumor immune infiltrate, which has not been seen following treatment with ‘not-α’ IL-2 and provides further mechanistic rationale for AB248’s differentiated anti-tumor activity. We look forward to initiating our first Phase 1 trial of AB248 in patients with solid tumors later this year.” New Preclinical Data for AB821, Asher Bio’s CD8-Targeted IL-21 In a poster presentation entitled, “AB821 is a CD8+ T cell selective IL-21 with enhanced bioavailability that mediates potent anti-tumor activity, cytotoxicity, and expansion of memory CD8+ T cells,” lead author Renee Greer, Ph.D., Senior Scientist at Asher Bio, described new preclinical data further characterizing AB821 relative to wild-type IL-21 in multiple in vitro and in vivo studies. The data show: “We are pleased to share new data on AB821, which support its continued development for the treatment of solid tumors,” said Dr. Greer. “Like IL-2, IL-21 derives its benefit from stimulating CD8+ T cells, but it does so via a distinct, potentially complementary, pathway. Whereas IL-2 agents, like AB248, drive T cell proliferation, AB821, an IL-21-based agent, can provide benefit through optimizing functionality of tumor-reactive CD8+ T cells. We look forward to advancing AB821 towards the clinic.” Both poster presentations will be available in the “Presentations and Posters” section of Asher Bio’s website: https://asherbio.com/pipeline/presentations-publications/ . About Asher Bio Asher Bio is a biotechnology company focused on developing therapies to precisely engage specific immune cells to fight cancer, chronic viral infection and autoimmune disease. We utilize our proprietary cis-targeting platform to develop therapies engineered to overcome limitations of other immune-based treatments by selectively activating specific immune cell types with validated disease fighting functionality. Our candidates feature an antibody connected to a modified immunomodulatory protein, such as a cytokine. Our candidate design is intended to enable our candidates to selectively activate the desired immune cells and not other cells that contribute to toxicity or immune suppression. Asher Bio was founded by Ivana Djuretic and Andy Yeung with support from Third Rock Ventures and is located in South San Francisco. For more information, please visit www.asherbio.com and follow us on Twitter @AsherBio and on LinkedIn . SOURCE: Asher Bio

ImmunotherapyAACR

10 Nov 2022

·www.biospace.com

Asher Bio Presents New Preclinical Data at SITC 2022 Further Supporting Advancement of AB248 and AB821 as Highly Differentiated Cis-targeted Cancer Immunotherapies

-- AB248 demonstrates non-clinical activity and safety pro its potential as a best-in-class IL-2 -- -- AB821 shows differentiated anti-tumor activity and enhanced bioavailability over wild type IL-21 -- -- On track to initiate Phase 1 trial of AB248 in 4Q 2022; Plan to new drug (IND) application for AB821 in 2H 2023 -- SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Asher Biotherapeutics, Inc. (Asher Bio), a biotechnology company focused on developing therapies to precisely engage specific immune cells to fight cancer, chronic viral infection, and autoimmune disease, today announced new preclinical data for AB248, its CD8-targeted interleukin-2 (IL-2) immunotherapy, and for AB821, its CD8-targeted interleukin-21 (IL-21) immunotherapy. The data will be presented at the Society for Immunotherapy in Cancer (SITC) 37th Annual Meeting, being held in Boston, Massachusetts, on November 8-12, 2022. “We are very pleased to share new data for both AB248 and AB821 at SITC, showcasing the power of our platform to efficiently generate product candidates that demonstrate highly selective T cell engagement, as well as differentiated pharmacodynamics, anti-tumor activity and tolerability across a range of in vitro and in vivo models,” said Ivana Djuretic, Ph.D., Chief Scientific Officer and Co-Founder of Asher Bio. “These data provide further validation that our cis-targeting approach enables us to activate only the desired immune cell type, potentially overcoming the pleiotropic effects that limited the clinical potential of previous immunotherapies. We look forward to advancing both programs as we aim to deliver on the promise of IL-2 and IL-21 as high-value targets to improve the care and treatment of people living with cancer.” New Preclinical Data for AB248, Asher Bio’s CD8-Targeted IL-2 In a poster presentation entitled, “CD8+ T cell selectivity of AB248 is essential for optimal anti-tumor activity and safety in nonclinical models,” lead author Kelly Moynihan, Ph.D., Senior Director and Project Team Leader at Asher Bio, described new preclinical data further differentiating AB248 from “not-α” IL-2 therapies and elucidating the mechanisms by which AB248 achieves enhanced anti-tumor activity and greater tolerability. The data show: AB248’s murine surrogate, muAB248, delivered strong anti-tumor activity without body weight loss, a general measure of tolerability, while a representative “not-α” IL-2 could not achieve meaningful activity without body weight loss. Selectivity for CD8+ T cells avoided expansion of other immune cells and, thereby, natural killer (NK) cell-driven toxicity and regulatory T cell (Treg)-mediated immunosuppression, while maximizing pharmacology on CD8+ T cells by avoiding the pharmacological sink comprised of other cells that express IL-2 receptors. Treatment with muAB248 demonstrated expansion of several CD8+ T cell subsets in the mouse tumor immune infiltrate, including stem-like, effector and memory CD8+ T cell subsets, which are distinct from effects of a representative “not-α” IL-2. In cynomolgus monkeys, repeat doses of AB248 selectively expanded CD8+ T cells by up to 20-fold, and AB248 was generally well-tolerated up to 1 mg/kg, with no adverse histopathology or clinical pathology findings at any dose level. “We are particularly encouraged to report new preclinical findings that underscore AB248’s differentiation from broadly acting IL-2-based therapies,” said Dr. Moynihan. “In addition to reinforcing the importance of selectively activating only CD8+ T cells for potentially improved safety and tolerability, new analyses presented at SITC suggest that AB248 may profoundly impact the tumor immune infiltrate, which has not been seen following treatment with ‘not-α’ IL-2 and provides further mechanistic rationale for AB248’s differentiated anti-tumor activity. We look forward to initiating our first Phase 1 trial of AB248 in patients with solid tumors later this year.” New Preclinical Data for AB821, Asher Bio’s CD8-Targeted IL-21 In a poster presentation entitled, “AB821 is a CD8+ T cell selective IL-21 with enhanced bioavailability that mediates potent anti-tumor activity, cytotoxicity, and expansion of memory CD8+ T cells,” lead author Renee Greer, Ph.D., Senior Scientist at Asher Bio, described new preclinical data further characterizing AB821 relative to wild-type IL-21 in multiple in vitro and in vivo studies. The data show: In STAT3 assays with human blood leukocytes, AB821 potently activated CD8+ T cells, with 1000-fold selectivity over other IL-21 target cell types, including B cells, NK cells and CD4+ T cells. In human CD8+ T cells, AB821 activity synergized with T cell receptor (TCR) stimulation to increase CD8+ T cell cytotoxic functionality and support T cell memory. AB821’s murine surrogate, muAB821, demonstrated potent single-dose monotherapy activity down to 0.1 mg/kg in MC38 colon cancer and T3 sarcoma tumor models, and showed synergistic anti-tumor activity with anti-PD1 therapy in multiple PD1-resistant tumor models. “We are pleased to share new data on AB821, which support its continued development for the treatment of solid tumors,” said Dr. Greer. “Like IL-2, IL-21 derives its benefit from stimulating CD8+ T cells, but it does so via a distinct, potentially complementary, pathway. Whereas IL-2 agents, like AB248, drive T cell proliferation, AB821, an IL-21-based agent, can provide benefit through optimizing functionality of tumor-reactive CD8+ T cells. We look forward to advancing AB821 towards the clinic.” Both poster presentations will be available in the “Presentations and Posters” section of Asher Bio’s website: . About Asher Bio Asher Bio is a biotechnology company focused on developing therapies to precisely engage specific immune cells to fight cancer, chronic viral infection and autoimmune disease. We utilize our proprietary cis-targeting platform to develop therapies engineered to overcome limitations of other immune-based treatments by selectively activating specific immune cell types with validated disease fighting functionality. Our candidates feature an antibody connected to a modified immunomodulatory protein, such as a cytokine. Our candidate design is intended to enable our candidates to selectively activate the desired immune cells and not other cells that contribute to toxicity or immune suppression. Asher Bio was founded by Ivana Djuretic and Andy Yeung with support from Third Rock Ventures and is located in South San Francisco. For more information, please visit and follow us on Twitter @AsherBio and on LinkedIn.

CollaborateAntibodyImmunotherapy

100 Deals associated with Denenicokin

External Link

KEGG	Wiki	ATC	Drug Bank
D09332	-	-	DB12908

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Melanoma recurrent	Phase 2	Canada	ZymoGenetics, Inc.	13 Dec 2007
Melanoma, Cutaneous Malignant	Phase 2	Canada	ZymoGenetics, Inc.	13 Dec 2007
Ovarian Cancer	Phase 2	France	Novo Nordisk A/S	04 Oct 2007
Ovarian Cancer	Phase 2	Germany	Novo Nordisk A/S	04 Oct 2007
Renal Cell Carcinoma	Phase 2	Germany	Novo Nordisk A/S	12 Jul 2007
Renal Cell Carcinoma	Phase 2	Netherlands	Novo Nordisk A/S	12 Jul 2007
Malignant melanoma stage IV	Phase 2	Australia	Novo Nordisk A/S	01 Sep 2004
Metastatic melanoma	Phase 2	Australia	Novo Nordisk A/S	01 Sep 2004
Metastatic Solid Tumor	Phase 1	United States	Bristol Myers Squibb Co.	01 Jun 2012
Unresectable Melanoma	Phase 1	United States	Bristol Myers Squibb Co.	01 Dec 2011

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


IAS2017	Not Applicable	-	15	IL-21-IgFc + IFNa-IgFc	kgtwxcojqe(pcwsrfrsvg) = jzczsqterl mvmyuvkjhe (shuaikefxo )	-	01 Jan 2017
				ART-only controls	kgtwxcojqe(pcwsrfrsvg) = arnqnvmaeq mvmyuvkjhe (shuaikefxo )
ACR2015	Not Applicable	Systemic Lupus Erythematosus	-	IL-21 (SLE T cells)	nbsfafelom(dwduaykrqz) = lphipimhid ibqcnmiwdp (vnsvrnqjai, 0.09) View more	-	10 Nov 2015
				IL-21 (HC T cells)	tvqlahgoup(onoawevsjk) = iisjhogiov ymvvwqfyos (buwlawxdxr, 45.28)
NCT01152788 (CTgov)	Phase 2	Metastatic melanoma	64	rIL-21 (rIL-21)	nnxprixrdl(kvoqouszcn) = hyeyoyvcfz zybmowpopv (etmlvzhgyv, gytcyerljn - gxzgtospbs) View more	-	21 Jul 2014
				Dacarbazine (Dacarbazine)	nnxprixrdl(kvoqouszcn) = fxasptttzx zybmowpopv (etmlvzhgyv, hkmtbnngnt - izojotdfjq) View more
SITC2014	Not Applicable	Melanoma Interleukin-21 (IL-21)	10	Melanoma-reactive CD8+ cytotoxic T lymphocytes (CTL) primed in the presence of Interleukin-21 (IL-21)	cklsxnupox(pafikjkigk) = lplapxsthm tllgnajoni (zghnmxvlln ) View more	Positive	24 Feb 2014
				Anti-CTLA4 blockade	umuphlqzaw(pocopaysil) = zlvtxxetbj jqlfuriszm (swbucfyvpu ) View more
ACR2012	Not Applicable	Rheumatoid Arthritis IL-21 \| RF-IgM \| RF-IgA ... View more	-	IL-21 (RA patients)	fmasfgojpq(zpawhkagsl) = zdlusidwfk xvbwvqmfrm (owjrcmbqxl ) View more	Positive	09 Nov 2012
				IL-21 (Healthy controls)	fmasfgojpq(zpawhkagsl) = tjoyanqcqd xvbwvqmfrm (owjrcmbqxl ) View more
EULAR2012	Not Applicable	Rheumatoid Arthritis rheumatoid factor (RF) \| anti-cyclic citrullinated peptide antibodies (anti-CCP)	-	IL-21 (RA patients)	jjsngwtikn(bgkajsnmtn) = dgpatmigtj dgjevxlkpy (bqhpxarxyk ) View more	-	06 Jun 2012
				IL-21 (Healthy controls)	jjsngwtikn(bgkajsnmtn) = egxtbdvuzj dgjevxlkpy (bqhpxarxyk ) View more
EULAR2010	Not Applicable	Systemic Lupus Erythematosus	-	IL-21 (Patients with SLE)	amkczggkmx(zfnjpfumsr) = uogsimourw zysysbburo (xxdstmcgka )	Positive	16 Jun 2010
ASCO2008	Phase 2	Malignant melanoma stage IV	24	rIL-21	sesqphgprf(asmroannep) = 4 nwsfbprbls (ubzsxsyjbt ) View more	-	20 May 2008
ASCO2007	Not Applicable	Chronic Lymphocytic Leukemia	-	Fludarabine and rituximab	eogtneozwy(rgxijsmsiv) = cikwsxmcyg iecnwcqces (bqnjcyhbqd )	-	20 Jun 2007
				IL-21	eogtneozwy(rgxijsmsiv) = edzqdbelkv iecnwcqces (bqnjcyhbqd )

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