First-in-Class: Cinda Biotech's TROP-2 ISAC Drug Clinical Trial Application

On December 19, the CDE official website displayed that Cinda Biotech's clinical trial application for the new class drug IBI3007 injection has been accepted.

IBI-3007 is Cinda's TROP-2-targeted ISAC (Immune Stimulatory Antibody Conjugates). This year, at AACR, Cinda presented its ISAC drug, a first-in-class TROP-2 ISAC that couples TLR7/8, enhancing the ADCP (antibody-dependent cellular phagocytosis) function. The technology platform is believed to originate from Bolt.

IBI-3007 has shown significant efficacy in vivo. In mouse transplant tumor models, a single dose of 5 mg/kg effectively inhibits tumor growth. Furthermore, when combined with a low dose of 1 mg/kg IBI-3007 and ADC, it also demonstrates good therapeutic effects.

Regarding safety, IBI-3007 shows good safety at a 5 mg/kg QW dose for two administrations, with much higher safety than Silverback's TLR7 ISAC. If allergic reactions occur after the second dose, a decrease in body temperature is observed. The highest dose administered can reach 45 mg/kg QW*2.

In monkey toxicology experiments, the HNSTD (Highest Non-Severe Toxic Dose) was 15 mg/kg for 4 doses via IV administration, with good pharmacokinetic data.

Immune Stimulator Antibody Conjugates (ISACs) are a type of antibody-drug conjugate (ADC) under the "Magic Bullets" concept, but unlike traditional ADCs that couple small molecule toxins, ISACs couple immune stimulators (e.g., TLR, STING, etc.).

The advantage of ISACs lies in directing immune stimulators to the tumor microenvironment via antibody drugs, where they are locally released. This resolves the challenge of systemic administration of immune stimulators and increases anti-tumor effects while avoiding systemic side effects. This potential has attracted considerable attention from pharmaceutical companies and has become a hot topic in R&D.

However, drug development is never easy, and the clinical trial results of ISACs have been less than ideal. Early-stage projects, such as Novartis', have already been discontinued.

Recently, Bolt Biotherapeutics announced in its Q1 2024 earnings report that it would discontinue the development of its core pipeline drug trastuzumab imbotolimod (BDC-1001) and lay off about 50% of its workforce. BDC-1001 is a TLR immune stimulatory antibody conjugate (ISAC), which targets HER2 through a non-degradable linker coupled with Bolt's proprietary TLR 7/8 dual agonist. It is worth noting that BDC-1001 was one of the fastest advancing immune stimulatory antibody conjugates globally and one of the most representative products in the ISAC class. The potential of ISAC drugs requires further exploration, and it is hoped that Cinda's differentiated ISAC drug target can achieve breakthroughs.