The editorial titled “Monotherapy of High-Grade Gliomas with a TGF-beta2 Targeting RNA Therapeutic" provides an overview regarding the development status, mechanism of action, and clinical potential of Mateon’s first-in-class RNA therapeutic OT101 for the treatment of the most aggressive brain tumors in adults.
Citation Reference: Uckun FM, Trieu VN. Monotherapy of High-Grade Gliomas with a TGF-beta2 Targeting RNA Therapeutic. Cancer Clin J. 2019; 1(1): 1007 (http://www.medtextpublications.com/open-access/monotherapy-of-high-grade-gliomas-with-a-tgfbeta2-targeting-rna-therapeutic-268.pdf)
The editorial titled “Convection-enhanced delivery of an anti-TGFbeta RNA therapeutic as a new therapeutic concept for children with diffuse intrinsic pontine glioma (“DIPG”)” explains a new concept for the treatment of pediatric DIPG patients with an RNA therapeutic targeting TGFbeta 2 and the scientific rationale and proof of concept data behind it.
Citation Reference: Uckun FM, Trieu VN. Convection-enhanced delivery of an anti-TGFbeta RNA therapeutic as a new therapeutic concept for children with diffuse intrinsic pontine glioma. Annals of
“These editorials emphasize our commitment to advance our investigational drug OT101 which shows high clinical impact potential to address unmet needs in neuro-oncology,” stated Dr. Trieu.
The research article "Recurrent or Refractory High-Grade Gliomas Treated by Convection-Enhanced Delivery of a TGFβ2-Targeting RNA Therapeutic: A Post-Hoc Analysis with Long-Term Follow-Up" was published in Cancers as part of the Special Issue Personalized Medicine: Recent Progress in Cancer Therapy and is available online:
HTML Version: https://www.mdpi.com/2072-6694/11/12/1892/htm
PDF Version: https://www.mdpi.com/2072-6694/11/12/1892/pdf
Special Issue: https://www.mdpi.com/journal/cancers/special_issues/PM_Cancers
Citation Reference: Uckun, F.M.; Qazi, S.; Hwang, L.; Trieu, V.N. Recurrent or Refractory High-Grade Gliomas Treated by Convection-Enhanced Delivery of a TGFβ2-Targeting RNA Therapeutic: A Post-Hoc Analysis with Long-Term Follow-Up. Cancers 2019, 11, 1892 (https://www.mdpi.com/2072-6694/11/12/1892/htm)
Dr. Uckun explained: “Our post-hoc analysis of the NCT00431561 Phase II clinical study outcome data demonstrates that the anti-TGFβ2 RNA therapeutic OT101 when intratumorally-administered via convection-enhanced delivery (CED) exhibits promising single-agent activity against recurrent or refractory (R/R) high-grade gliomas (HGG). Most importantly, OT101 induced durable complete response (CR), partial response (PR) and stable disease (SD) in more than one third of the efficacy population. In the objective responders, OT101 displayed a previously not reported pattern of single agent activity, which was characterized by (i) slow but robust tumor size reductions; (ii) very often, an early onset transient increase of tumor edema and/or pseudo-progression which preceded the tumor size reductions; and (iii) late-onset objective responses that were achieved at a median of 287 days. To our knowledge, this is the first demonstration that the intratumoral delivery of an RNA therapeutic via extended CED in the absence of other therapeutic agents or radiation results in >3 year median PFS and >3.5 year OS in greater than one third of the efficacy population in a R/R HGG trial. It will be important to evaluate OT101 in difficult-to-treat IDH-wildtype, MGMT-unmethylated R/R HGG patients who have failed a temozolomide-based first line adjuvant therapy, as they have a dismal prognosis and are in urgent need for new and effective salvage therapies. Intratumorally administered OT101 exhibited a promising safety profile, but some CED procedure and device-related potential complications were also identified. Therefore, risk mitigation strategies, especially preventive methods aimed at reducing the risk of infections, will be employed in future trials to further improve the potential patient benefit of intratumoral OT101 therapy.”
OT101, a first-in-class RNA therapeutic designed to abrogate the immunosuppressive actions of TGF-beta 2, is Oncotelic’s lead anti-brain tumor drug candidate. In a completed Phase 2 clinical study, OT-101 exhibited clinically meaningful single-agent activity and induced durable complete and partial responses in recurrent and refractory adult high-grade glioma patients, including adults with GBM. DIPG, an orphan disease with a low survival rate and no established or effective standard of care. Despite numerous clinical trials of chemotherapeutic agents, immuno-oncology drugs and specific targeted therapies, no significant progress has been made in the treatment of DIPG and the prognosis remains dismal, with a mean OS of 9–12 months from the time of diagnosis, a median survival time of approximately 10 months, and a two-year OS rate of less than 10 percent. Five-year survival is less than 3 percent, and many long-term survivors have evidence of moderate or severe cognitive impairment, likely as a consequence of radiation therapy. Chemotherapy does not have an established role in the management of patients with DIPG. Furthermore, there is no standard treatment for progressive DIPG after the failure of radiation therapy and no salvage regimen has been shown to extend survival. Therefore, there is an urgent need for therapeutic innovations for treatment of DIPG, as reflected by multiple treatment modalities being evaluated in early neuro-oncology clinical trials. Further development of OT-101 may offer renewed hope for salvage therapy not only for adult high-grade glioma patients but also for pediatric DIPG patients. Last month,
Mateon was created by the recent reverse merger with Oncotelic which became a wholly owned subsidiary of
About Mateon’s Lead Product Candidate, OT101
High-grade gliomas (HGG) are characterized by a T-cell exhaustion signature and pronounced T-cell hyporesponsiveness of their tumor microenvironment (TME). Transforming growth factor beta 2 (TGFB2) has been implicated as a key contributor to the immunosuppressive landscape of the TME in HGG. OT101, a first-in-class RNA therapeutic designed to abrogate the immunosuppressive actions of TGFB2, is Oncotelic’s lead anti-brain tumor drug candidate. OT101 has been granted orphan designation by the
Mateon's Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this communication regarding strategy, future operations, future financial position, prospects, plans and objectives of management are forward-looking statements. Words such as “may”, “expect”, “anticipate” “hope”, “vision”, “optimism”, “design”, “exciting”, “promising”, “will”, “conviction”, "estimate," "intend," "believe", “quest for a cure of cancer”, “innovation-driven”, “paradigm-shift”, “high scientific merit”, “impact potential” and similar expressions are intended to identify forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about future plans, the progress, timing, clinical development, scope and success of future clinical trials, the reporting of clinical data for the company’s product candidates and the potential use of the company’s product candidates to treat various cancer indications. Each of these forward-looking statements involves risks and uncertainties and actual results may differ materially from these forward-looking statements. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, clinical trial site activation or enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, failure of collaborators to support or advance collaborations or product candidates and unexpected litigation or other disputes. These risks are not exhaustive, the company faces known and unknown risks, including the risk factors described in the company’s annual report on Form 10-K filed with the
Source: Mateon Therapeutics