Jacobio Pharma Presented Preliminary Results from a Phase I Trial of Jab-8263 at ASH 2024

Preliminary Results from Phase I Trial of JAB-8263, a BET Inhibitor, in Myelofibrosis (MF) were Presented at ASH 2024

Jacobio Pharma shared promising early data from a Phase I trial of JAB-8263, a potent bromodomain and extra-terminal (BET) inhibitor, for treating intermediate- or high-risk myelofibrosis (MF) at the 2024 ASH Meeting.

Bromodomain and extra-terminal (BET) proteins are key regulators of epigenetic mechanisms influencing inflammation and oncogenic processes.

Preliminary Results of Patients with Myelofibrosis (MF) from a Phase I Trial of Jab-8263, a Potent BET Inhibitor

Authors: Junyuan Qi, Bo Jiang, Wei Yang, Xudong Wei, Hongmei Jing, Yongping Song, Andrea Wang-Gillam, Yuli Ding, Chao Bi, Ting Zhang

The data demonstrated that JAB-8263 was well-tolerated, with a recommended Phase 2 dose (RP2D) of 0.3 mg once daily. Early efficacy results for JAB-8263 as a monotherapy in MF are encouraging, showing significant reductions in spleen volume (SVR) and improvements in total symptom scores (TSS) among most patients.

As of October 17, 2024, 16 patients with intermediate- or high-risk MF had been enrolled, and 13 patients had undergone at least one post-treatment efficacy evaluation:

– Patients experienced a mean SVR of -19.95% at week 24, with a best response of -26.16%.
– Two patients achieved SVR reductions of ≥35%, with one patient reaching -34.9%.
– At week 24, 60% (6/10) of patients experienced a ≥50% reduction in TSS.
– Among JAK inhibitor-pretreated patients, the best SVR responses were -41.2% and -34.9%.
– Half (3/6) of these JAK inhibitor-pretreated patients achieved a TSS50 at week 24.

“These preliminary results underscore the potential of our potent BET inhibitor in addressing MF. We remain committed to exploring additional indications for JAB-8263, striving to bring new hope to cancer patients worldwide.” – said Dr. Andrea Wang-Gillam, Chief Medical Officer and Global Head of R&D at Jacobio.

Andrea Wang-Gillam at ASH24 

Methods

In the dose-escalation phase of this trial, patients with intermediate- or high-risk myelofibrosis (MF) were administered JAB-8263 at doses ranging from 0.125 mg to 0.4 mg once daily (QD). Eligibility criteria included an ECOG performance status (PS) ≤ 2, splenomegaly (spleen volume ≥ 450 cm³), and a Dynamic International Prognostic Scoring System (DIPSS) score of intermediate-1 or higher.

Primary objectives of the phase 1 portion were to assess safety, tolerability, and establish the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Secondary objectives included spleen volume reduction (SVR) and total symptom score (TSS) improvements at 24 weeks.

Results

As of July 11, 2024, 12 patients with intermediate- or high-risk MF were enrolled across four dose levels (0.125 mg: 1 patient; 0.2 mg: 2 patients; 0.3 mg: 6 patients; 0.4 mg: 3 patients). Most participants (11/12) had a JAK2 mutation, and 58.3% (7/12) had received prior JAK inhibitor therapy.

Dose-limiting toxicities (DLTs) were observed in one patient at the 0.4 mg dose, including grade 3 elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Common treatment-related adverse events (TRAEs), occurring in over 20% of patients, included increases in ALT, AST, and bilirubin, as well as prolonged prothrombin time.

Grade 3 TRAEs were observed in 8.3% of patients, including ALT and AST increases and a decrease in blood fibrinogen. JAB-8263 was generally well tolerated, with no treatment discontinuations due to TRAEs.

At the time of reporting, 11 patients remained on active treatment, and 10 had undergone at least one post-treatment efficacy evaluation. Across all patients, the mean SVR was -25.84% (range: -7.1% to -56.5%), with two patients achieving an SVR ≥ 35%. Additionally, 30% of patients experienced a ≥ 50% reduction in TSS (TSS50) by week 12, increasing to 55.6% by week 24.

Among the seven patients with prior JAK inhibitor therapy, the mean SVR was -19.86% at week 12 and -20.33% at week 24.

This subgroup also demonstrated symptom improvement, with a mean TSS reduction of -22% at week 12 and -41% at week 24. Half of the JAK inhibitor-experienced patients achieved TSS50 by week 24.

Preliminary data suggest that JAB-8263 is well tolerated in patients with MF, with grade 3 TRAEs observed in 16.7% of participants and no discontinuations due to adverse events. Promising efficacy signals, including SVR and symptom improvement, were observed, particularly in patients with prior JAK inhibitor exposure.

About Jacobio Pharma

Jacobio Pharma (1167.HK) is dedicated to innovating and delivering breakthrough therapies. Its pipeline targets six major signaling pathways, including KRAS, immune checkpoints, tumor metabolism, P53, RB, and MYC.

The company aims for global leadership in drug R&D, with key projects positioned among the top three worldwide. With R&D centers in Beijing, Shanghai, and Boston, Jacobio leverages its Induced Allosteric Drug Discovery Platform (IADDP) and iADC Platform to accelerate therapeutic innovation.

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