Pipeline
Milciclib
NSCLC
Deprioritized
Overview
Milciclib is a potent, small molecule inhibitor of multiple cyclin-dependent kinases (CDKs), tropomycinreceptor kinases and Src family kinases controlling cell growth and malignant progression of cancer. Milciclib has demonstrated safety and tolerability in 316 patients with advanced solid cancers in Phase 1 and 2 studies and also exhibited positive clinical responses. In two, successfully completed, Phase 2 thymic cancer trials, Milciclib successfully increased overall survival and met both primary and secondary endpoints.
In July and September 2019, we reported positive Phase 2a safety, tolerability and efficacy data of Milciclib as a monotherapy in 28 patients with advanced HCC. The results, presented at ASCO2020, warrant further clinical development. Strong genetic and pharmacological evidence suggests that pan-CDKs inhibitors might have potential to suppress the multiple tumorigenic pathways that are activated due to activation of KRAS gene. Clinical data from a Phase I dose-escalation study with combination of milciclib with gemcitabine showed significant disease stabilization and suggested that milciclib can reverse gemcitabine-resistance in NSCLC refractory solid tumors. The clinical response in the NSCLC patient was particularly very promising. Company is exploring the combination of milciclib and gemcitabine in NSCLC subjects with pan KRAS-positive mutations.
In inflamation, IL-6 levels increase 100 – 1000x favouring IL-6 TRANS-signaling conditions
Milciclib inhibits CDKs and Kinases
Clinical trials
Phase 2a Clinical Trial (CDKO-125a-010) for Milciclib as a Monotherapy for the Treatment of HCC
Completed a Phase 2a trial (CDKO-125a-010) of Milciclib safety and tolerability as a single therapy in sorafenib-resistant patients with HCC (https://clinicaltrials.gov/ct2/show/NCT01011439). 28 out of 31 treated patients were evaluable, 14 completed the 6-month duration study. Nine patients were approved to continue treatment under compassionate use by their respective ethical committees. Oral treatment with Milciclib was well-tolerated with manageable toxicities. No drug-related deaths were recorded. The most frequent drug-related adverse events such as: diarrhea, nausea, retinal hemorrhage, fatigue, asthenia, chills, ataxia, headache, rash.
MAJOR HIGHLIGHTS OF THE CLINICAL DATA
Primary endpoint: Safety
Treatment was well-tolerated and adverse events were manageable with no drug related deaths in the trial
Secondary endpoints: Efficacy
- Median Time-to-Progression was 5.9 months
- Patients with stable disease – 57%
- Patients showed clinical benefit response – 61%