Last update 24 Jun 2024

Roginolisib

Last update 24 Jun 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

[6-Fluoro-1-(4-morpholin-4-ylmethyl-phenyl)-5,5-dioxo-4,5-dihydro-1H-5Lambda6-thiochromeno[4,3-c]pyrazol-3-yl]-morpholin-4-yl-methanone hemi-fumarate, Roginolisob, IOA 244

+ [1]

Target

PI3Kδ

Mechanism

PI3Kδ inhibitors(Phosphatidylinositol 3 kinase delta inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesImmune System Diseases+ [4]

Active Indication

Chronic Lymphocytic LeukemiaNon-Small Cell Lung CancerPeripheral T-Cell Lymphoma+ [6]

Inactive Indication-

Originator Organization

iOnctura SAStartup

Active Organization

iOnctura SAStartup

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

Structure

Molecular FormulaC26H27FN4O5S

InChIKeyNFHSJYKXENYICE-UHFFFAOYSA-N

CAS Registry1305267-37-1

Clinical Trials associated with Roginolisib

NCT04328844 / Active, not recruitingPhase 1

First-in-Human Dose Study of IOA-244 Alone and in Combination With Pemetrexed/Cisplatin in Patients With Advanced or Metastatic Cancers

The objective of study IOA-244-101 is to determine whether IOA-244 is safe and tolerable in cancer patients (Part A). In addition, the study will assess whether IOA-244 can increase the anti-tumour immune response in patients both as monotherapy and in combination pemetrexed/cisplatin/avelumab (Part B Mesothelioma and NSCLC 1st line), in combination with avelumab (Part B Cutaneous Melanoma and NSCLC 2nd/3rd line) and ruxolitinib (Part B Primary Myelofibrosis)

Start Date25 Feb 2020

Sponsor / Collaborator

iOnctura SAStartup

100 Clinical Results associated with Roginolisib

100 Translational Medicine associated with Roginolisib

100 Patents (Medical) associated with Roginolisib

Literatures (Medical) associated with Roginolisib

01 Dec 2023·Journal of Taibah University Medical Sciences

Molecular properties and In silico bioactivity evaluation of (4-fluorophenyl)[5)-3-phen-(4-nitrophenyl yl-4,5-dihydro-1H-pyrazol-1-yl]methanone derivatives: DFT and molecular docking approaches

Article

Author: Ayobami, Odunola O ; Banjo, Semire ; Felix, Latona D ; Kolawole, Oyebamiji A ; Omotayo, Ibrahim A ; Olasegun, Abdulsalami I ; Emmanuel, Oladuji T ; Dele, Owonikoko A ; Dasola, Adeoye M

Objectives:

Molecular structures, spectroscopic properties, charge distributions, frontier orbital energies, nonlinear optical (NLO) properties and molecular docking simulations were analyzed to examine the bio-usefulness of a series of (4-fluorophenyl)[5-(4-nitrophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]methanone derivatives.

Methods:

The compounds were studied through computational methods. Equilibrium optimization of the compounds was performed at the B3LYP/6-31G(d,p) level of theory, and geometric parameters, frequency vibration, UV-vis spectroscopy and reactivity properties were predicted on the basis of density functional theory (DFT) calculations.

Results:

The energy gap (ΔEg), electron donating/accepting power (ω-/ω+) and electron density response toward electrophiles/nucleophiles calculated for M1 and M2 revealed the importance of substituent positioning on compound chemical behavior. In addition, ω-/ω+ and ΔEn/ΔEe indicated that M6 is more electrophilic because of the presence of two NO₂ groups, which enhanced its NLO properties. The hyperpolarizability (β₀) of the compounds ranged from 5.21 × 10^-30 to 7.26 × 10^-30 esu and was greater than that of urea; thus, M1-M6 were considered possible candidates for NLO applications. Docking simulation was also performed on the studied compounds and targets (PDB ID: 5ADH and 1RO6), and the calculated binding affinity and non-bonding interactions are reported.

Conclusion:

The calculated ω^- and ω⁺ indicated the electrophilic nature of the compounds; M6, a compound with two NO₂ groups, showed enhanced effects. Molecular electrostatic potential (MEP) analysis indicated that amide and nitro groups on the compounds were centers of electrophilic attacks. The magnitude of the molecular hyperpolarizability suggested that the entire compound had good NLO properties and therefore could be explored as a candidate NLO material. The docking results indicated that these compounds have excellent antioxidant and anti-inflammatory properties.

01 Dec 2023·International journal of toxicology

Non-Clinical Toxicology Evaluation of the Novel Non-ATP Competitive Oral PI3 Kinase Delta Inhibitor Roginolisib

Article

Author: van der Veen, Lars ; Lahn, Michael ; Deken, Marcel A ; Schmitt, Michael

Roginolisib (IOA-244) is a novel, non-ATP competitive phosphoinositide-3-kinase (PI3K) delta inhibitor that regulates Akt/mTOR signaling. Roginolisib was administered once daily to rats and dogs in dose-range finding (DRF) and 4-week GLP toxicology studies. Free plasma levels of roginolisib exceeded the cellular target engagement IC90 for PI3Kδ for ≥12 hours at doses of 5 mg/kg, the IC90 for PI3Kβ for ≥2 hours at doses ≥15 mg/kg, and the IC50 for PI3Kα for ≥2 hours at dose levels ≥45 mg/kg. Toxicity in rats occurred at doses ≥100 mg/kg. In dogs, we observed dose-dependent skin and gastrointestinal toxicity and doses ≥30 mg/kg had a greater incidence of mortality. Lymphoid tissue toxicity occurred in both species. Toxicities in dogs observed at the ≥15 mg/kg dose, affecting the digestive mucosa, liver, and skin, cleared after treatment cessation. Doses ≤75 mg/kg were tolerated in rats and the no-observed-adverse-effect-level (NOAEL) in rats was 15 mg/kg. Due to mainly epithelial lesions of the skin at 5 mg/kg and necrotizing damage of the intestinal epithelia at ≥15 mg/kg, no NOAEL was determined in dogs. However, the adverse effects observed in dogs at 5 mg/kg were considered monitorable and reversible in patients with advanced malignancies. Furthermore, the PK profile subsequently proved to be a decisive factor for achieving selective PI3Kδ inhibition without the toxicities observed in dogs. As the result of the unique PK profile of roginolisib, patients were able to take daily roginolisib without dose modification and showed pharmacodynamic PI3Kδ inhibition over several months without gastrointestinal or dermatologic toxicities.

01 Sep 2023·Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry

Interactions of arene ruthenium(II) complexes [η⁶-(C₆H₆)Ru(pprip)Cl]⁺ and [η⁶-(C₆H₆)Ru(H₂iiP)Cl]⁺ with RNA triplex poly(U)•poly(A)*poly(U).

Article

Author: Yuan, Feng ; Tan, Lifeng ; Liu, Xiaohua ; Li, Juan

Two arene ruthenium(II) complexes [η⁶-(C₆H₆)Ru(pprip)Cl]PF₆ (Ru1; pprip = 2-(3-phenyl-1H-pyrazol-4-yl)-imidazolo[4,5-f][1,10]phenanthroline) and [η⁶-(C₆H₆)Ru(H₂iiP)Cl]PF₆ (Ru2; H₂iiP = 2-(indole-3-yl)-imidazolo[4,5-f][1,10]phenanthroline) have been synthesized and characterized in this work. Binding properties of Ru1 and Ru2 with the triplex RNA poly(U)•poly(A)*poly(U) were investigated by spectrophotometry and spectrofluorometry as well as viscosimetry. Analysis of spectroscopic titrations and viscosity measurements show that the two complexes bind with the triplex through intercalation, while the binding affinity for Ru2 toward the triplex is stronger than that for Ru1. Melting experiments indicate that the stabilizing effects of Ru1 and Ru2 toward the triplex differ from each other. Under the conditions used herein, Ru1 only stabilizes the Hoogsteen base-paired strand (third strand) without affecting stabilization of the Watson-Crick base-paired strand (the template duplex) of the triplex, while Ru2 stabilizes both the template duplex and the third strand. Although the two complexes prefer to stabilizing the third strand rather than the template duplex, the third-strand stabilization effect of Ru2 is stronger than that of Ru1. The obtained results of this work reveal that the planarity of the intercalative ligands plays an important role in the triplex stabilization by arene Ru(II) complexes.

News (Medical) associated with Roginolisib

20 Jun 2024

·www.prnewswire.com

iOnctura announces EUR80 million Series B financing to progress pipeline through Phase II trials

Led by new investor Syncona, with participation from the European Innovation Council Fund as well as existing investors To progress pipeline of innovative, first-in-class, oral cancer treatments targeting neglected and hard-to-treat cancers To accelerate development of lead asset roginolisib for treatment of uveal melanoma and a number of other oncology indications GENEVA and AMSTERDAM, June 20, 2024 /PRNewswire/ -- iOnctura, a clinical-stage biopharmaceutical company combating neglected and hard-to-treat cancers, today announces that it has closed an EUR80 million Series B financing. The funding round was led by new investor Syncona Limited with participation by the EIC Fund, the venture arm of the European Innovation Council (EIC), as well as existing investors M Ventures, Inkef Capital, VI Partners, Schroders Capital and 3B Future Health Fund. iOnctura is developing a portfolio of precision oral small molecules that target cancers in novel ways. The bold new treatments extend lives and improve healthspans, changing the outlook for patients and their families. The Company has progressed two therapeutic candidates into mid-stage clinical development. Lead asset roginolisib is the first allosteric modulator of PI3Kδ, with a unique chemical structure and binding mode. It is being developed for indications burdened by immune mediated resistance and a high expression of PI3Kδ in cancer cells and tumor-infiltrating immune cells. Roginolisib has potential to become the first successful, clinically meaningful therapy to target the critical PI3Kδ cancer pathway. It has demonstrated an unprecedented and first-in-class clinical profile in solid and hematological malignancies, with over 48 patients treated to date. The financing will be used to accelerate development of roginolisib for the treatment of uveal melanoma (UM), a rare cancer of the eye with few available treatments. Eye melanoma is a rapidly growing market which is projected to be worth USD 9.56B by 2032[1] . In a Phase Ib clinical trial, roginolisib demonstrated long-term safety and promising efficacy in UM with sustained clinical activity over many months. Full results will be announced in the coming months. The successful UM data reported so far, combined with a rich preclinical data package, supports the rationale to expand into other indications. iOnctura plans to commence trials in other cancer indications, including non-small cell lung cancer and primary myelofibrosis, later in 2024. iOnctura's second clinical asset, cambritaxestat, is the only autotaxin inhibitor in clinical development to treat cancer. It has excellent potency and specificity, and is being developed for highly fibrotic tumors that overexpress autotaxin. A Phase Ib study of cambritaxestat in combination with chemotherapy in metastatic pancreatic cancer is ongoing. Catherine Pickering, Chief Executive Officer, iOnctura, said: "This financing is validation of iOnctura's approach to developing precision cancer treatments with maximum clinical impact. These therapies have the potential to significantly prolong the healthspan of patients suffering with neglected cancer types, such as uveal melanoma. We are pleased to welcome our new investors Syncona and the EIC Fund alongside our existing strong syndicate. Their experience will be invaluable as we look to advance our pipeline and take iOnctura to its next stage of growth." Roel Bulthuis, Managing Partner and Head of Investments at Syncona and Board member of iOnctura, added: "iOnctura represents a compelling opportunity to invest in line with our strategy and capital allocation focus in a clinical-stage company, and take a promising lead programme through to late-stage development. To date, no company has been able to successfully target this well-known cancer pathway with sufficient precision. By allosterically modulating PI3Kδ, iOnctura has achieved a new level of precision and could be the first company to develop a clinically meaningful medicine targeting this pathway. Its programmes have potential utility across a range of cancers, which we are supporting the company to unlock through a refined clinical strategy." About iOnctura iOnctura is a clinical-stage biopharmaceutical company combating neglected and hard-to-treat cancers with precision oral small molecules that target cancers in novel ways. The bold new treatments extend lives and improve healthspans, changing the outlook for patients and their families. Two therapeutic candidates have progressed into mid-stage clinical development: roginolisib is the first allosteric modulator of PI3Kδ and cambritaxestat is the only autotaxin inhibitor in clinical development to treat cancer. iOnctura BV is headquartered in Amsterdam, The Netherlands with its wholly owned Swiss subsidiary, iOnctura SA, located in Geneva, Switzerland. iOnctura is backed by specialist institutional investors including Syncona, EIC Fund, M Ventures, Inkef Capital, VI Partners and Schroders Capital. About roginolisib Roginolisib is the first allosteric modulator of PI3Kδ with a unique chemical structure and binding mode. The PI3K signalling pathway is one of the most commonly dysregulated pathways in cancer and the precise targeting of the PI3Kδ isoform delivers substantial anti-tumor effects with a low-toxicity profile. Clinical data have demonstrated roginolisib's excellent safety profile and sustained clinical activity in uveal melanoma (UM), a rare eye cancer with few available treatments. Randomized Phase II trials are planned to start in late 2024 in UM and other cancers, including non-small cell lung cancer and primary myelofibrosis. About cambritaxestat Cambritaxestat is a first-in-class autotaxin inhibitor that has shown preclinically to inhibit the growth and proliferation of cancer cells, stimulate immune cell infiltration and inhibit the development of fibrosis. It offers a new therapeutic approach for treating highly fibrotic hard-to-treat tumors such as pancreatic cancer. A Phase Ib study of cambritaxestat in combination with chemotherapy in metastatic pancreatic cancer is ongoing. [1] Emergen Research, Jan 2024 SOURCE iOnctura

Phase 1Phase 2Clinical Result

20 Jun 2024

·firstwordpharma.com

With fresh €80M in hand, iOnctura looks to chart new PI3K path

Shaking off the baggage that has weighed down the PI3K class, iOnctura announced Thursday that it secured €80 million ($86 million) in a series B round to help move its lead asset roginolisib – an allosteric modulator of PI3Kδ that could offer more selective targeting and possibly a cleaner safety profile – into Phase II.The fundraise was led by new investor Syncona and joined by the European Innovation Council (EIC) Fund. "To date, no company has been able to successfully target this well-known cancer pathway with sufficient precision," commented Roel Bulthuis, head of investments at Syncona, adding iOnctura "could be the first company to develop a clinically meaningful medicine targeting this pathway."Existing backers such as M Ventures, Inkef Capital, VI Partners, Schroders Capital and 3B Future Health Fund also contributed.A class with baggageThe PI3K class, well known for its toxic side effects when used to treat blood cancers, has faced a wave of market withdrawals in recent years due to a combination of poor tolerability, modest efficacy and competitive pressures. In 2022, the FDA convened an advisory panel that voted in favour of requiring future approvals of PI3K inhibitors to be supported by randomised trial data with active comparator arms, rather than the single-arm studies on which early PI3K drug approvals had been based."Roginolisib is very different from what's gone before," iOnctura CEO Catherine Pickering told FirstWord. It targets PI3Kδ "in an allosteric way, which translates to precision targeting of PI3Kδ only," she said, adding, "we are on target at the maximum… [without inhibiting] anything else in our patients."The company says the compound has demonstrated an "unprecedented" clinical profile in solid and haematological malignancies, with over 48 patients treated to date. According to Pickering, the precision targeting has led to a favourable safety profile, with no dose interruptions or significant adverse events typically associated with PI3Kδ inhibition. "We see minor Grade 1 and one or two Grade 2 side effects, but nothing to speak of," she said, adding that the company will be publishing the data in the coming weeks.Phase II-bound this yearThe series B financing will accelerate development of roginolisib in its lead indication of uveal melanoma, where a Phase Ib study demonstrated sustained clinical activity "over many months" in this setting. The company said Phase II testing in that disease setting is set to begin in late 2024, as well as in non-small-cell lung cancer and primary myelofibrosis. Pickering suggested the mid-stage uveal study may even potentially support an accelerated approval.Second projectMeanwhile, iOnctura’ssecond clinical asset, cambritaxestat, is an autotaxin inhibitor in clinical development for cancer. The candidate, which was brought in from Cancer Research UK as a discovery-stage project, is being developed for highly fibrotic tumours that overexpress autotaxin. A Phase Ib study in combination with chemotherapy in metastatic pancreatic cancer is ongoing.Pickering highlighted the potential of cambritaxestat to break down the fibrotic stromal shell that "protects" tumours, but also its ability to aid immune cell penetration. "By inhibiting and taking down the levels of LPA (lysophosphatidic acid) in the tumour microenvironment – not only taking this fibrotic core away – you're also allowing immune cells to penetrate the tumour. So, it's more than just an anti-fibrotic," she explained.

Phase 1Phase 2Clinical Result

20 Jun 2024

·www.pharmaceutical-technology.com

iOnctura raises nearly $86m in Series B to fund Phase II cancer trials

Syncona was the major investor in iOnctura having invested €30m ($32.2m) for a 23% stake in the company. Image Credit: eamesBot / Shutterstock. Swiss biopharma iOnctura has raised €80m ($85.8m) in Series B financing to fund the Phase II clinical trials for its two lead cancer therapies, roginolisib and cambritaxestat. The company plans to start clinical trials investigating roginolisib in various cancer indications including non-small cell lung cancer (NSCLC) and primary myelofibrosis, later this year. Roginolisib is an allosteric modulator of a phosphoinositide 3-kinase delta (PI3Kδ), which induces an immune response by signalling the growth and division proliferation of white blood cells. PI3Kδ is also overexpressed in multiple haematological cancers where its hyperactivity is associated with tumour progression and invasive potential. In January, roginolisib received an orphan drug designation from the US Food and Drug Administration (FDA). The PI3K class of drugs have faced a setback in recent years after the FDA’s Oncologic Drugs Advisory Committee (ODAC) unanimously recommended that “future approvals of PI3K inhibitors for hematologic malignancy indications be supported by randomised trial data”, in 2022. The decision was based on high levels of fatal adverse events (AEs) and high rates of toxicity associated with the drug class. Roginolisib is being evaluated in a Phase I clinical trial (NCT04328844) as a monotherapy and in combination with chemotherapy in patients with advanced or metastatic cancers, including metastatic uveal melanoma, a rare eye cancer. Of the 23 metastatic uveal melanoma patients treated with 80mg roginolisib, less than 5% showed Grade 3 or 4 toxicities. The therapy has an overall survival (OS) rate of 70%, with median OS not being reached. See Also: SGNB-7H4V by Pfizer for Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer (HER2- Breast Cancer): Likelihood of Approval SGNB-7H4V by Pfizer for Epithelial Ovarian Cancer: Likelihood of Approval Cambritaxestat is an autotaxin inhibitor, which controls the secretion of extracellular lysophosphatidic acid that regulates a variety of cell responses including proliferation and death. It is being developed for the treatment of highly fibrotic tumours that overexpress autotaxin, such as metastatic pancreatic cancer. The therapy’s safety and pharmacokinetics are being evaluated in a Phase I/II study (NCT05586516) in patients with metastatic pancreatic cancer. The trial’s primary endpoint is the incidence of treatment-emergent side effects over a year. The Series B investors included Syncona Limited and the EIC Fund, the venture arm of the European Innovation Council (EIC), along with Merck Ventures, Inkef Capital, VI Partners, Schroders Capital and 3B Future Health Fund. UK-based Syncona invested €30m ($32.2m) for a 23% stake in iOnctura. Concurrent with iOnctura funding, Syncona also invested £16.5m ($21m) for a 60.9% stake in Series A to Yellowstone, a University of Oxford-spinout biologics company. Yellowstone is developing soluble bispecific T cell receptor-based therapeutics against acute myeloid leukaemia.

Phase 1Orphan DrugPhase 2Clinical Result

100 Deals associated with Roginolisib

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hematologic Neoplasms	Phase 2	-	iOnctura SAStartup	31 May 2023
Solid tumor	Phase 2	-	iOnctura SAStartup	31 May 2023
Chronic Lymphocytic Leukemia	Phase 2	GB	iOnctura SAStartup	-
Non-Small Cell Lung Cancer	Phase 2	GB	iOnctura SAStartup	-
Peripheral T-Cell Lymphoma	Phase 2	GB	iOnctura SAStartup	-
Primary Myelofibrosis	Phase 2	GB	iOnctura SAStartup	-
Uveal Melanoma	Phase 2	GB	iOnctura SAStartup	-
Hodgkin's Lymphoma	Phase 1	IT	iOnctura SAStartup	25 Feb 2020
Hodgkin's Lymphoma	Phase 1	GB	iOnctura SAStartup	25 Feb 2020
Myelofibrosis	Phase 1	IT	iOnctura SAStartup	25 Feb 2020

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESMO_IO2023	Not Applicable	-	-	Roginolisib 80 mg	ldoyxsubbc(nvlbnkmkrj) = ebiqofunei cnmnuikmym (tgoexucjca )	-	07 Dec 2023
NCT04328844 (FiH dose escalation study, ICML2023)	Phase 2	Follicular Lymphoma	8	Roginolisib 80 mg QD	jgrrulkhfy(azgivrhizc) = takurfzdtw zvfnojppbh (uhysccshan ) View more	Positive	09 Jun 2023
EHA2023	Not Applicable	Refractory Follicular Lymphoma	8	Roginolisib 20 mg QD	xidioexymm(fyzcgfjoxj) = AST/ALT elevation (G3) were observed in 2/8 pts zlvwhlmqjj (ypvzjwnizf ) View more	-	08 Jun 2023
				Roginolisib 80 mg QD
NCT04328844 (DIONE-01, ASCO2023) Manual	Phase 1	Uveal Melanoma \| Advanced cancer	24	Roginolisib (Part A: pts with solid tumours and Follicular Lymphoma)	edjwuhbuhr(xrelptqxoe) = roginolisib 80 mg QD fhyopsyfcc (xohvayoxcr ) View more	Positive	26 May 2023
				Roginolisib (Part A(dose escalation): UM pts)
NCT04328844 (ASCO2022) Manual	Phase 1	Advanced cancer	23	IOA-244 (Part A Solid Tumor (completed))	wpwajbokuw(wdergistjq) = xwogxvkbwh gvymxhxyas (eqfbybovua )	Positive	02 Jun 2022
				IOA-244 (Uveal Melanoma Pts (progressed ≥1 line prior therapy))	mfbwqadojd(bezxvwkxaw) = ptjdobftgk nqdlmaqysj (xwvdadymwp ) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

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

view full example data

Get started for free today!

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

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Roginolisib

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation