J&J's $850M Autoimmune Dual-Antibody Acquisition Unveiled: PX128 (IL-13/TSLP) Shows Picomolar Potency and Extended Half-Life

Mar 21, 2025 20:00 CST Updated 20:00

Johnson & Johnson

Medical Device R&D and Manufacturer

Proteologix

Immune Disease Drug Developer

Author｜Bio-three

On May 16, 2024, Johnson & Johnson announced an $850 million cash acquisition of Proteologix, with the potential for additional milestone payments, causing a sensation. At that time,Proteologix's R&D pipeline includes only two bispecific antibodies, PX128 (IL-13/TSLP) and PX130 (IL-13/IL-22), with the former being at the stage of imminent clinical entry.

Johnson & Johnson Acquires Proteologix Press Release (Johnson & Johnson Official Website)

Recently, the PCT patent (WO2025049345) for Proteologix's PX128 was published. This highly expensive product has finally been unveiled for the first time, allowing the industry to take a close look at this IL-13/TSLP bispecific antibody.

The TSLP antibody component of PX128 adoptsHybridoma Technology for ScreeningMultiple high-affinity clones were obtained through the TSLP reporter gene method, among which 51B2 was selected for further humanization based on its differentiated epitope from Tezepelumab, an already marketed TSLP antibody.

TSLP Antibody Epitope Detection of PX128 (WO2025049345)

After humanization, the TSLP antibody hz51B2-L3H9 reached the upper limit of Biacore for binding detection of human TSLP antibody, with a detection value of 1.24 pM, and its binding ability to monkey TSLP was 86.6 pM.

TSLP Antibody Affinity Detection for PX128 (WO2025049345)

The antibody portion of IL-13 is modified from Amgen's IL-13 antibody patent US7585500.(Application in November 2005) A C34Y mutation was introduced into the light chain CDR1 region of a specific antibody, resulting in the formation of the 73P1 antibody, which demonstrated an increased affinity for both human IL-13 and monkey IL-13 compared to before the modification.

IL-13 Antibody Affinity Detection of PX128 (WO2025049345)

In terms of IL-13 signaling, it first binds to IL-13Rα1, then IL-4Rα is recruited to form a ternary complex.Based on the biological functions of IL-13, Proteologix categorized the epitopes of IL-13 antibodies into two types: the first type simultaneously blocks IL-13Rα1 and IL-13Rα2, while the second type blocks the formation of a ternary complex between IL-13 and IL-4Rα. The latter is considered to have better clinical efficacy.

Comparison of IL-13 neutralizing activity with two marketed IL-13 antibodies showed that 73P1 and the marketed antibody Ab#2, which has a class II epitope, exhibited similar blocking activity, suggesting that the epitope of 73P1 belongs to class II.

Neutralizing Activity Assay of PX128's IL-13 Antibody (WO2025049345)

In the construction of bispecific antibody drugs, Proteologix has adopted various forms,Ultimately, an asymmetric form was adopted.The heavy chain part adopts the "knob-in-hole" structure to prevent mismatch, with the TSLP antibody part using the "hole" structure and the IL-13 antibody adopting the "knob" structure. To prevent light chain mismatch, the CH1/CL charge pair method is utilized. Additionally, the heavy and light chains of the IL-13 antibody have undergone various mutations in forms such as R2, JT11, and JT7.

The bispecific antibody structure design of PX128 (WO2025049345)

In vitro TSLP and IL-13 reporter gene activity assays showed that different forms of mutants, such as R2, JT11, and JT7, all exhibited neutralizing activity against TSLP and IL-13, with JT11 demonstrating the highest activity.

In Vitro Activity Assay of PX128 (WO2025049345)

The results of detecting IL-13-induced CCL17 production levels in human peripheral blood mononuclear cells (PBMCs) showed that both PX128-JT11 and PX128-JT7 exhibited strong inhibitory effects at picomolar levels, superior to the combined effect of TSLP and IL-13.

Under the effect of half-life extension using LS mutation, PX128-JT11 and PX128-JT7 demonstrated more prolonged inhibitory effects, indicating that the extension of PK contributes to the improvement of PD effects.

In Vitro Activity Assay of PX128 (WO2025049345)

Based on the above in vitro results, PX128-JT11 was further optimized and selected for pharmacokinetic testing in cynomolgus monkeys. The results showed that the half-life of PX128-JT11 reached 26 days.Significantly superior to Sanofi's clinical-stage IL-13/TSLP dual antibody lunsekimig, it also has advantages in terms of compliance in the future.

Pharmacokinetic Testing of PX128 in Cynomolgus Monkeys (WO2025049345)

Johnson & Johnson, as a leader in the autoimmune field, has deep积累 in traditional areas such as rheumatoid arthritis and psoriasis. However, its growth has shown signs of fatigue, and it primarily adopts combination therapy for the development of next-generation treatments.Facing the rapid rise of novel autoimmune fields such as atopic dermatitis, Johnson & Johnson evidently needs to focus on more innovative therapies, which might also be the main reason for its acquisition of two preclinical bispecific antibodies from Proteologix.

Johnson & Johnson's Autoimmune Drug Development Landscape (Johnson & Johnson Official Website)

On the other hand, facing fierce competition in next-generation drug development, Proteologix has chosen to iterate on mature targets while not blindly pursuing novelty or flashiness in its technology platform. Instead, it has focused on delving into biological mechanisms, utilizing established antibody engineering techniques to rapidly develop competitive new drugs, which have garnered favor from large pharmaceutical companies. This approach may well become a model for biotech firms to emulate.

Co-Build Biomedical Innovation Ecosystem!

How to Join BiG Membership?