【Company Research】I-Mab BioPharma (IMAB US) – Lemzoparlimab, a highly differentiated anti-CD47 mAb with superior safety and efficacy

• Promising phase 1 data of lemzoparlimab (TJC4) at the 2020 SITC Annual Meeting. This phase 1 is a first-in-human study (NCT03934814) in the US evaluating lemzoparlimab for the treatment of relapsed or refractory solid tumors and lymphoma. The trial includes two parts. The first part is comprised of a single agent dose escalation followed by two separate combination regimens in an escalating dose range (Part 1b with pembrolizumab; Part 1c with rituximab). The second part is a dose expansion study in the combination therapies. The data released at SITC 2020 is the single agent dose escalation in first part. Recruitment of patients for the dose escalation study of lemzoparlimab in combination with pembrolizumab or rituximab is ongoing.

 

• Outstanding safety, pharmacokinetics (PK) and efficacy data among peers. As a highly differentiated CD47 antibody designed to minimize inherent binding to normal red blood cells while preserving its strong anti-tumor activity, lemzoparlimab’s initial results demonstrate differentiated safety and PK profile and efficacy signal. Safety: Lemzoparlimab is well tolerated as a single agent at a dose range from 1mg/kg to 30 mg/kg without introducing any priming dosing strategy. In all DLT-evaluable patients, no dose-limiting toxicities or severe hematologic adverse events were observed. As an important indicator to evaluate a CD-47 antibody, anemia occurred 30% with no >grade 3 anemia. PK: PK of lemzoparlimab appears to be linear at mid to high dose levels following a single dose with no significant "sink effect", which means the bioavailability of lemzoparlimab could maintain even when elevating the dose. Efficacy: Among the total 16 evaluable patients, one confirmed partial response (PR) was observed in a metastatic melanoma patient in the 30 mg/kg monotherapy cohort (N=3), who had failed prior systemic treatment of nivolumab and ipilimumab. Three patients achieved SD, including one subject in 1mg/kg cohort, one subject in 10mg/kg and one in 30mg/kg cohort. According to the data, lemzoparlimab achieved 33.3% ORR and 66.6% DCR in the 30 mg/kg monotherapy cohort (N=3), which is very encouraging efficacy signal.

 

• Early mover advantages and significant synergies from the global strategic partnership with AbbVie. I-Mab reached a broad, global collaboration agreement with AbbVie for the development and commercialization of lemzoparlimab. We also expect significant clinical synergies between I-Mab's lemzoparlimab and AbbVie's Venclexta (Venetoclax, a Bcl-2 inhibitor) and other transformative therapies. I-Mab is conducting a phase I trial of lemzoparlimab for AML/MDS in China which has finished 20mg/kg in dose escalation, and the trial may be finished by 1Q21. In addition, I-Mab continues to advance the Ph1 combination study of lemzoparlimab with Keytruda for the treatment of solid tumors and with Rituxan for the treatment of patients with lymphoma in the US. We expect Lemzoparlimab to enter into Phase 2 trials in the US and China by mid-2021E, indicating significant early-mover advantages for the drug.

   

• Maintain BUY. We maintain our DCF-based TP unchanged at US$52.57 (WACC: 10.6%, terminal growth rate: 3.0%).