ARNT

– NKT2152, a highly potent, selective and orally bioavailable small molecule HIF2 α inhibitor, is being evaluated in combination with the standard-of-care regimen of atezolizumab and bevacizumab in the first-line treatment of patients with advanced or metastatic Hepatocellular Carcinoma (HCC) compared to atezolizumab and bevacizumab alone – NKT2152’s broad anti-tumor activity in several xenograft models supports investigation of its role in tumor types beyond clear cell Renal Cell Carcinoma (ccRCC) WILMINGTON, DE, USA I January 21, 2025 I NiKang Therapeutics ® Inc. (“NiKang”), a clinical-stage biotech company focused on developing innovative small molecule oncology medicines to bring transformative therapies to patients in need, today announced that the first patient has been dosed in the global randomized phase 1b/2 clinical study evaluating NKT2152, a highly potent, selective and orally bioavailable small molecule HIF2α inhibitor, in combination with standard-of-care regimen of atezolizumab (Tecentriq®) and bevacizumab (Avastin®) in the first-line treatment of patients with advanced or metastatic HCC. This study is being conducted under a clinical trial collaboration with F. Hoffmann-La Roche Ltd (“Roche”) as part of Roche’s MORPHEUS-liver platform trial (NCT04524871). “The commencement of this randomized study of NKT2152 in partnership with Roche represents a significant milestone in the advancement of NKT2152 for the treatment of tumors beyond ccRCC,” said Zhenhai Gao, Ph.D., co-founder, president, and CEO of NiKang. “NKT2152 has demonstrated significant anti-tumor efficacy and a favorable safety profile not only in human ccRCC patients but also in preclinical xenograft models of solid tumors beyond ccRCC, underscoring its potential for broad application in human cancer treatments. HCC is of particular interest due to the compelling scientific rationale supporting NKT2152 and robust preclinical data. With high potency, selectivity, and unique human pharmacokinetic (PK) profile characterized by higher systemic exposure, a larger volume of distribution, and a longer half-life, NKT2152 emerges as an ideal candidate for combination with antibody-based regimens to treat solid tumors beyond ccRCC, where higher drug exposure may be necessary. We are enthusiastic about further exploring NKT2152’s potential in the first-line treatment of HCC patients through this randomized trial”. About NKT2152 NKT2152 is a potent, selective and orally available small molecule HIF2α inhibitor which binds to HIF2α allosterically and disrupts the HIF2α/HIF1β transcription factor complex, thereby reducing the production of proteins which lead to tumorigenesis. NKT2152 is currently under evaluation in a Phase 1/2 clinical study in ccRCC as a single agent (NCT05119335) and a Phase 2 clinical study in ccRCC in combination with palbociclib and sasanlimab (NCT05935748). A third clinical study, as part of Roche’s MORPHEUS-liver platform trial, evaluating the combination with standard-of-care atezolizumab and bevacizumab in first-line unresectable/advance hepatocellular carcinoma (HCC) (NCT04524871) is ongoing. About NiKang Therapeutics NiKang Therapeutics is a clinical-stage biotech company focused on discovering and developing innovative small molecule oncology medicines to bring transformative therapies to patients in need. Our target selection is driven by deep insight into disease biology and molecular pathways. Our discovery approach is informed by target structure biology and capitalizes on structure-based drug design. The successful implementation of our strategy enables us to rapidly and efficiently discover and advance proprietary drug candidates with the most desirable pharmacological features into clinical studies. We have successfully advanced three programs into clinical trials, including NKT2152 (HIF2α), NKT3447 (CDK2), and NKT3964 (CDK2). For more information, please visit http://www.nikangtx.com SOURCE: Nikang Therapeutics

WILMINGTON, Del.--( BUSINESS WIRE )--NiKang Therapeutics ® Inc. (“NiKang”), a clinical-stage biotech company focused on developing innovative small molecule oncology medicines to bring transformative therapies to patients in need, today announced that the first patient has been dosed in the global randomized phase 1b/2 clinical study evaluating NKT2152, a highly potent, selective and orally bioavailable small molecule HIF2α inhibitor, in combination with standard-of-care regimen of atezolizumab (Tecentriq®) and bevacizumab (Avastin®) in the first-line treatment of patients with advanced or metastatic HCC. This study is being conducted under a clinical trial collaboration with F. Hoffmann-La Roche Ltd (“Roche”) as part of Roche’s MORPHEUS-liver platform trial (NCT04524871). “ The commencement of this randomized study of NKT2152 in partnership with Roche represents a significant milestone in the advancement of NKT2152 for the treatment of tumors beyond ccRCC,” said Zhenhai Gao, Ph.D., co-founder, president, and CEO of NiKang. “ NKT2152 has demonstrated significant anti-tumor efficacy and a favorable safety profile not only in human ccRCC patients but also in preclinical xenograft models of solid tumors beyond ccRCC, underscoring its potential for broad application in human cancer treatments. HCC is of particular interest due to the compelling scientific rationale supporting NKT2152 and robust preclinical data. With high potency, selectivity, and unique human pharmacokinetic (PK) profile characterized by higher systemic exposure, a larger volume of distribution, and a longer half-life, NKT2152 emerges as an ideal candidate for combination with antibody-based regimens to treat solid tumors beyond ccRCC, where higher drug exposure may be necessary. We are enthusiastic about further exploring NKT2152’s potential in the first-line treatment of HCC patients through this randomized trial”. About NKT2152 NKT2152 is a potent, selective and orally available small molecule HIF2α inhibitor which binds to HIF2α allosterically and disrupts the HIF2α/HIF1β transcription factor complex, thereby reducing the production of proteins which lead to tumorigenesis. NKT2152 is currently under evaluation in a Phase 1/2 clinical study in ccRCC as a single agent (NCT05119335) and a Phase 2 clinical study in ccRCC in combination with palbociclib and sasanlimab (NCT05935748). A third clinical study, as part of Roche’s MORPHEUS-liver platform trial, evaluating the combination with standard-of-care atezolizumab and bevacizumab in first-line unresectable/advance hepatocellular carcinoma (HCC) (NCT04524871) is ongoing. About NiKang Therapeutics NiKang Therapeutics is a clinical-stage biotech company focused on discovering and developing innovative small molecule oncology medicines to bring transformative therapies to patients in need. Our target selection is driven by deep insight into disease biology and molecular pathways. Our discovery approach is informed by target structure biology and capitalizes on structure-based drug design. The successful implementation of our strategy enables us to rapidly and efficiently discover and advance proprietary drug candidates with the most desirable pharmacological features into clinical studies. We have successfully advanced three programs into clinical trials, including NKT2152 (HIF2α), NKT3447 (CDK2), and NKT3964 (CDK2). For more information, please visit http://www.nikangtx.com Tecentriq® (atezolizumab) and Avastin® (bevacizumab) are registered trademarks of Genentech, a member of the Roche Group.

The Aryl Hydrocarbon Receptor (AHR) is a transcriptional regulatory factor in cells that can bind to ligands. Normally, AHR exists in the cytoplasm, forming a complex with various companion proteins. However, upon binding with a ligand, AHR enters into the cell nucleus through the nuclear pore and forms a dimer with the Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT). This formed dimer can bind with the Xenobiotic response element (XRE) in DNA, promoting the expression of downstream genes. In the nucleus, AHR can also bind with other transcription factors, thereby affecting the expression of genes regulated by the bound transcription factors. Among the proteins regulated by the AHR signaling pathway, the cytochrome P450 superfamily is the most thoroughly researched. The activation of AHR can directly trigger the expression of proteins like CYP1A1, CYP1A2, and these enzymes play a crucial role in the metabolism of aromatic compounds: they are responsible not only for the metabolism of exogenous toxic substances but also impact the biotransformation of various drugs. AHR acts as a sensor for cells to perceive the external environment, with high expression in barrier cells and certain immune cells. The AHR signaling pathway has also been proven to be a key signaling pathway in the regulation of the immune system. AHR agonists have shown effects in some representative models of autoimmune diseases (including systemic lupus erythematosus, Behcet's syndrome, multiple sclerosis, inflammatory bowel disease, etc.). AHR Competitive LandscapeAccording to the data provided by Patsnap Synapse-Global Drug Intelligence Database: the following figure shows that as of 4 Sep 2023, there are a total of 19 AHR drugs worldwide, from 28 organizations, covering 22 indications, and conducting 49 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. The analysis of target AHR reveals a competitive landscape with multiple companies actively involved in the development of drugs targeting AHR. Roivant Sciences Ltd., Guangdong Zhiguang Biotechnology Co. Ltd., and Shenzhen Tianji Pharmaceutical Co Ltd. are among the fastest-growing companies in this field. The indications for AHR-related drugs cover a wide range of diseases, including psoriasis, dermatitis, inflammatory bowel diseases, neoplasms, and more. Small molecule drugs and chemical drugs are the most rapidly progressing drug types, indicating intense competition in the development of innovative drugs.  China has shown progress in the development of AHR-related drugs, alongside the United States, which remains the leading country in this field. Overall, the target AHR presents a promising area for pharmaceutical development with diverse indications and active research and development efforts worldwide. Approved AHR agonists for market launch：BenvitimodBenvitimod is a small molecule drug developed by Guangdong Zhonghao Pharmaceutical Co. Ltd. It is primarily used for the treatment of immune system diseases, congenital disorders, and skin and musculoskeletal diseases. The drug targets the AHR, which plays a crucial role in regulating immune responses and inflammation. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. The active indications for Benvitimod include plaque psoriasis, psoriasis, dermatitis, and atopic dermatitis. These conditions are characterized by chronic inflammation and abnormal immune responses, leading to symptoms such as redness, itching, and scaling of the skin. By targeting the AHR, Benvitimod aims to modulate the immune system and reduce inflammation, providing relief to patients suffering from these conditions. Benvitimod has received approval for use in both global and Chinese markets. The drug obtained its first approval in China in May 2019, making it available to patients in the country. The approval process for Benvitimod involved special review projects and priority review, indicating the potential significance and urgency of the drug in addressing the unmet medical needs of patients with immune system diseases and skin disorders. As a small molecule drug, Benvitimod offers several advantages in terms of formulation, administration, and potential for oral delivery. Small molecule drugs are typically easier to manufacture and have a well-established regulatory pathway for approval. This may contribute to the drug's successful development and approval in both global and Chinese markets. AHR agonists entering into phase I clinical trials：AT-177AT-177 is a small molecule drug that is being developed by Azora Therapeutics, Inc. It is designed to target the AHR and is intended for the treatment of digestive system disorders. The drug is currently in Phase 1 of clinical development, which is the earliest stage of testing in humans. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. The therapeutic areas that AT-177 is focused on are digestive system disorders, specifically colitis and ulcerative colitis. Colitis refers to inflammation of the colon, while ulcerative colitis is a chronic inflammatory bowel disease that affects the colon and rectum. These conditions can cause symptoms such as abdominal pain, diarrhea, and rectal bleeding. Being in Phase 1 of clinical development means that AT-177 is still in the early stages of testing in humans. Phase 1 trials are typically conducted with a small number of healthy volunteers or patients to evaluate the safety, dosage, and potential side effects of the drug. These trials are important for determining the appropriate dosage and identifying any potential risks or adverse reactions. In summary, AT-177 is a small molecule drug being developed by Azora Therapeutics, Inc. for the treatment of digestive system disorders, specifically colitis and ulcerative colitis. It is currently in Phase 1 of clinical development, and its target is the AHR. Further research and clinical trials will be necessary to assess the drug's potential effectiveness and safety.