Envafolimab(KN035)* is an investigational PD-L1 antibody currently being evaluated in broad clinical studies in the US, China, and Japan. It is created by a fusion of the of PD-L1 domain antibody with the Fc domain of a regular antibody. Compared with conventional PD-(L)1 antibodies currently approved and under development, KN035’s unique design makes a differentiated and competitive profile: better tumor tissue penetration in animal model studies, subcutaneous injectable, high affinity and stability, low immunogenicity, mutated Fc domain to eliminate ADCC/CDC activity, and comparable in vivo half-life.

Envafolimab is the world’s first subcutaneously injectable PD-L1 inhibitor. Patients can complete administration within 30 seconds, making it particularly suitable for frail, elderly patients and those with adverse reactions to intravenous infusions. It also holds the potential for at-home self-administration, thereby significantly improving patients' quality of life.

KN026* is an anti-HER2 bispecific antibody invented by Alphamab Oncology using the proprietary Fc-based heterodimer bispecific platform technology called CRIB (Charge Repulsion Induced Bispecific). KN026 can bind two non-overlapping epitopes of HER2 simultaneously, leading to a dual HER2 signal blockade. KN026 has demonstrated potentially superior efficacy compared with Trastuzumab and Pertuzumab in combination, as well as better tumor inhibition in HER2-positive tumor cell lines. Additionally, KN026 has also shown inhibitory effect on tumor cells with medium or low HER2 expression or Trastuzumab-resistant cell lines.

KN026 received IND approval from the National Medical Products Administration (NMPA) of China and U.S. Food and Drug Administration (FDA) in 2018. Currently, several pivotal clinical trials of KN026 for the second-line treatment of gastric cancer (GC)/ gastroesophageal junction cancer (GEJ), the first line treatment of HER2-positive breast cancer (BC), neoadjuvant treatment for HER2-positive BC are being conducted. Additionally, combination therapies with bispecific antibodies and bispecific antibody-drug conjugates (BADC) are being explored.

The results of multiple clinical studies in different stages showed that KN026 has good efficacy and safety profiles, even in heavily pretreated patients with HER2-positive BC and GC. KN026 in combination with chemotherapy for the treatment of patients with HER2-positive GC (including GEJ) who have failed first-line standard treatment was granted breakthrough therapy designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China (NMPA).

JSKN003 is an anti-HER2 biparatopic antibody-drug conjugate (ADC), which is developed inhouse with Alphamab’s proprietary Glycan-specific conjugation platform. The antibody molecule KN026 is site-specifically modified via enzyme catalytic reaction and click chemistry to achieve a drug-to-antibody ratio (DAR) of approximately 4. JSKN003 can bind HER2 on the surface of tumor cells and release topoisomerase I inhibitors (TOPIi) through cellular endocytosis, thereby exert anti-tumor effects.

Compared with its ADC counterparts, JSKN003 demonstrated better serum stability and stronger bystander effect, which effectively expands the therapeutic window. JSKN003 shows good safety profile and efficacy in preclinical studies in both high and low HER2- expression models (CDX+PDX).

JSKN016 is a bispecific antibody conjugated drug (ADC) targeting HER3 (Human epidermal growth factor receptor 3) and TROP2 (Trophoblast cell surface antigen 2), which is developed inhouse with proprietary Glycan-specific conjugation platform.

After binding with TROP2 and/or HER3 on the surface of tumor cells, JSKN016 enters the lysosome through target-mediated endocytosis, releasing cytotoxic topoisomerase I inhibitor (TOPIi), and then inducing apoptosis of TROP2 and/or HER3 positive tumor cells. In addition, the inhibitor can penetrate the cell membrane and enter the antigen-negative tumor cells to exert bystander effect. These effects can effectively inhibit the growth of tumor cells.

KN046 is the world's first recombinant humanized PD-L1/CTLA-4 bispecific antibody independently developed by Jiangsu Alphamab. Its innovative designs include: a proprietary CTLA-4 domain antibody with a significantly improved safety profile; a bispecific antibody fused with PD-L1 antibody; engineered to target the tumor microenvironment with high PD-L1 expression, and Treg clearing function.

There are about 20 clinical trials of KN046 in different stages covering more than 10 types of tumors including NSCLC, pancreatic cancer, thymic cancer, HCC, ESCC and TNBC in Australia, the US and China. The results of these clinical trials have shown an advantage in survival for patients. Alphamab Oncology has received FDA clearance to enter phase II trial of KN046 based on the clinical results in China and Australia. Moreover, KN046 has obtained the U.S. FDA's orphan drug designation for thymic epithelial tumor in September 2020. Several pivotal clinical trials are currently being conducted, among which the interim analysis of the phase III clinical study of KN046 combined with chemotherapy as the first-line treatment of NSCLC successfully met the prespecified PFS endpoint.

KN019 is a biosimilar of Belatacept (Nulojix®), an immunosuppressive agent approved for prophylaxis of organ rejection in adult patients receiving a kidney transplant. As a fusion protein composed of the Fc-fragment of a human IgG1 immunoglobulin linked to the extracellular domain of CTLA-4, Belatacept acts as a selective T cell co-stimulation blocker. Belatacept’s superior efficacy profile has been demonstrated in long-term outcome studies*.

Belatacept is an improved version of Abatacept (Orencia®) with higher potency. Orencia is approved for rheumatoid arthritis, idiopathic arthritis, and psoriatic arthritis.

KN019 has started phase II trial for rheumatoid arthritis in August 2019 and will expand to oncology-related indications in the future.

Due to its structure of a fusion protein with complex glycosylation, Belatacept is very difficult to manufacture as the biosimilar product. So far, few companies are able to develop a competitive biosimilar of Belatacept. In contrast, KN019 has demonstrated robust CMC and superior quality in multiple batches of large-scale production.