FDA Grants Orphan Drug Designation to LBL-034 in Multiple Myeloma

• LBL-034 has received orphan drug designation from the FDA for the treatment of patients with multiple myeloma.
• LBL-034 is a humanized, bispecific T–cell-engaging antibody targeting GPRC5D and CD3.
• The agent is currently undergoing evaluation in a phase 1/2 trial (NCT06049290) for the treatment of patients with relapsed/refractory multiple myeloma.

LBL-034, a humanized bispecific T–cell-engaging antibody targeting GPRC5D and CD3, has been granted orphan drug designation by the FDA for the treatment of multiple myeloma.¹

This bispecific antibody binds to CD3 on T cells and the tumor-associated antigen GPRC5D on myeloma cells, thereby activating T cells to target and kill cancer cells.

As the third GPRC5D-targeted CD3 T-cell engager in clinical development, LBL-034 demonstrates superior binding affinity for GPRC5D, increased potency, and a reduced risk of T-cell exhaustion and cell death compared with other agents in this class.

Microscopic photorealistic image of myeloma cells - Generated with Google Gemini AI

“I am pleased to see the positive progress in our development of the new medications to benefit patients with rare diseases like multiple myeloma. Multiple myeloma remains an incurable malignancy and with the increasing lines of treatment, the interval between the tumor relapses will become shorter and shorter, and eventually it will evolve into relapsed/refractory multiple myeloma, which seriously threatens human life and health,” said Charles Cai, MD, PhD, chief medical officer of Leads Biolabs, in a press release. “It is urgent to develop new and more effective treatment options. LBL-034 adopts a unique molecular design, and the preliminary clinical results indicate its promising antitumor efficacy and safety. We will expedite the clinical development of LBL-034 and strive to bring safe and effective treatment options to multiple myeloma patients around the world as early as possible.”

LBL-034 is currently being evaluated in a first-in-human, open-label, multicenter, dose-escalation and dose-expansion phase 1/2 trial (NCT06049290) in patients with relapsed/refractory multiple myeloma.² The trial, which received investigational new drug (IND) approval from both the Chinese National Medical Products Administration on July 20, 2023, and the FDA on July 28, 2023, was launched in China in 2023.¹

This clinical trial consists of 2 parts: a phase 1 dose-escalation and dose-expansion study, followed by a phase 2 efficacy study. The phase 1 study will assess the safety and tolerability of LBL-034 and determine the recommended phase 2 dose. The phase 2 study will evaluate the efficacy of LBL-034 in treating relapsed/refractory multiple myeloma and includes 2 treatment arms. The trial aims to enroll between 66 and 418 patients across both phases.

Enrollment is open to patients aged 18 years and older with an ECOG performance status of 0 or 1, documented initial diagnosis of multiple myeloma according to International Myeloma Working Group diagnostic criteria, and a life expectancy of at least 12 weeks.

The primary end points of the study include objective response rate, dose-limiting toxicities, and maximum tolerated dose. The secondary end points are pharmacokinetics, immunogenicity, minimal residual disease, and duration of response.

Early data from the study have shown promising efficacy and a favorable safety profile. Preliminary results are expected to be presented at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition.^3,4

In preclinical studies presented at the 2023 ASH Annual Meeting, LBL-034 demonstrated robust T-cell dependent cytotoxicity in GPRC5D-positive cells across a range of expression levels, as well as increased expression of CD25 and CD69 and cytokine release, including IFN-γ, TNF-α, IL-6. Notably, LBL-034 exhibited minimal binding to CD3 and limited cytokine release in the absence of GPRC5D-expressing cells.

In additional preclinical models, LBL-034 showed potent antitumor activity even at low doses. These doses included 1 mg/kg in the MC38-GPRC5D syngeneic model and 0.3 mg/kg in the NCI-H929 xenograft model.

Toxicology studies have also previously revealed that repeated intravenous doses of LBL-034 at 5 mg/kg, 15 mg/kg, and 50 mg/kg, administered weekly for up to 5 cycles, were well tolerated. Pharmacological, pathological, and biochemical analyses determined the no-observed-adverse-effect-level of LBL-034 to be 50 mg/kg.

“LBL-034 is the first product from Leads Biolabs to receive orphan drug designation from FDA, marking a successful step for us on this challenging but meaningful journey. Taking this opportunity, we will further optimize our pipeline layout, broaden our exploration boundaries in the biopharmaceutical field, and provide innovative solutions for more unmet medical needs,” added Xiaoqiang Kang, MD, PhD, founder, chairman, and chief executive officer of Leads Biolabs, in the press release.¹

REFERENCES:

1. Leads Biolabs receives orphan drug designation from the US FDA for LBL-034, a uniquely designed, highly differentiated anti-GPRC5D/CD3 bispecific antibody, for the treatment of multiple myeloma. News release. Nanjing Leads Biolabs Co., Ltd. November 6, 2024. Accessed November 6, 2024. https://tinyurl.com/2fjezyah

2. A phase I/II clinical trial of LBL-034 in patients with relapsed refractory multiple myeloma. ClinicalTrials.gov. Updated April 17, 2024. Accessed November 6, 2024. https://clinicaltrials.gov/study/NCT06049290

3. Key preclinical data on LBL-034, a uniquely designed, highly differentiated bispecific antibody targeting GPRC5D will be presented at the 65th American Society of Hematology (ASH) Annual Meeting. News release. Leads Biolabs. December 8, 2023. Accessed November 6, 2024. https://tinyurl.com/5ymxz7ac

4. Wang B, Huang X, Sun J, et al. LBL-034, a highly differentiated T-cell engaging bispecific antibody targeting GPRC5D for the treatment of relapsed or refractory multiple myeloma. Blood. 2023;142(suppl 1):4672. doi:10.1182/blood-2023-181395