FWD1509, A Targeted Therapy For Certain EGFR/HER2 Mutants, Is Cleared For Ph1 By NMPA

▎Content Team Report on WuXi AppTec

According to the latest public disclosure by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration, FWD1509, a 4th generation small molecule EGFR-targeted drug independently developed by Forward Pharma has been approved for clinical trials in China for the treatment of advanced non-small cell lung cancer (NSCLC). FWD1509 is an orally-administered small molecule EGFR-targeted drug and also Forward Pharma's first Class 1 innovative drug.

In response to this, Dr. Zhu Chenggang, Chief Scientific Officer (CSO) of Forward Pharma, stated in a recent interview with WuXi AppTec's content team, "The approval of FWD1509 for clinical trials in China following its approval in the United States in January this year represents another important R&D milestone. This also means that Forward Pharma 's R&D pipelines have entered the clinical development stage in both China and the United States and will concurrently conduct Phase 1/2 clinical trials.

As we all know, EGFR has become a mature target in the field of lung cancer drug development. It is a cell surface receptor of the epidermal growth factor family with tyrosine kinase activity. After activation, it activates downstream signaling pathways including PI3K-Akt, MAPK-Erk, etc., producing cell proliferation effects. Abnormal activation of EGFR can activate genes related to tumor proliferation and differentiation, thereby inducing the formation and development of tumors.

Tyrosine kinase inhibitors (TKIs) targeting this target can compete with endogenous ligands to bind to EGFR, inhibit tyrosine kinase activation, block the EGFR signaling pathway, thereby inhibiting tumor cell proliferation, metastasis, and promoting tumor cell apoptosis. Currently, there are three generations of EGFR-TKIs approved for marketing clinically, which can target most mutation types such as L858R, exon 19-del, and T790M drug resistance mutations, bringing significant benefits to most EGFR mutant lung cancer patients.

However, clinical medicine still faces significant challenges. "Many patients will develop resistance 1-2 years after using existing drugs. Moreover, there are many types of EGFR mutations, and effective treatment methods are still lacking for some rare mutations. Exon 20 insertion mutation is one of the largest categories, accounting for about 10% of EGFR primary mutations. There is still an unmet need in the clinic," said Dr. Zhu Chenggang.

FWD1509 developed by Forward Pharma is designed to meet this clinical need. It is a small molecule EGFR irreversible inhibitor. Preclinical studies have shown that it not only exhibits strong inhibitory activity against common EGFR mutations (L858R, exon19-del) and drug-resistant mutations (T790M), but also strongly inhibits various types of EGFR exon 20 insertion mutations.

It is reported that in multiple preclinical studies, FWD1509 can effectively inhibit the proliferation of lung cancer cells with various subtypes of EGFR exon20 insertion mutations, demonstrating excellent anti-tumor efficacy. At the same time, it also shows significant efficacy for HER2 exon 20 insertion mutations. Moreover, this candidate drug can efficiently penetrate the blood-brain barrier and is expected to be used in the treatment of brain metastases of various EGFR mutated non-small cell lung cancers.

"What is particularly noteworthy is that FWD1509 has excellent selectivity for wild-type EGFR, making it an ideal treatment window. With its excellent inhibitory activity against various EGFR exon 20 insertion mutations, ideal safety and ability to penetrate the blood-brain barrier, it is expected to be developed into a best-in-class drug targeting EGFR exon 20 insertion mutations and provide new treatment options for patients with these types of tumors." said Dr. Zhu Chenggang.

He further pointed out that with the continuous development of science and technology, the research on targets in the field of drug development is becoming more and more in-depth and precise, and the clinical demand and expectations for targeted drugs are also increasing, especially in terms of drug safety. The non-small cell lung cancer field has many targets, and in recent years, targeted therapies and immunotherapies have been approved, contributing to improving the quality of life of patients. However, the challenges that not yet been solved clinically cannot be ignored, and the research field needs to continue to seek solutions.

"On the one hand, we need to continue to explore the mechanisms of cancer drug resistance; on the other hand, we also need to continue to broaden the discovery of new targets. In addition, this includes new treatment methods, new combination therapy models, as well as new signaling pathways and exploration of targeted drugs, etc. These are all directions that need further efforts and are the areas that Forward Pharma has always been committed to researching." said Dr. Zhu Chenggang.

Forward Pharma was founded in 2015, with Dr. Xu Liangliang as the CEO and Dr. Zhu Chenggang as the Chief Scientific Officer. The company's Chinese R&D headquarters is located in Nanshan, Shenzhen, and international operating and R&D teams have been set up in Shanghai and Shenzhen, focusing on the fields of oncology and autoimmunity, developing new generation small molecule drugs and antibody-targeted drugs.

Currently, Forward Pharma has established a research and development pipeline including 5 candidate drugs. Among them, FWD1509 is its first Type 1 new drug to enter clinical development and received FDA clinical approval in January of this year. Patient enrollment for its Phase 1 clinical trial has been launched synchronously.

In addition, Forward Pharma ' other investigational drugs include: FWD1802, a third-generation selective oral estrogen receptor degrader for the treatment of breast cancer; FWB1313, an IL-13-specific monoclonal antibody for the treatment of severe asthma and atopic dermatitis; FWB2114, a new target monoclonal antibody for the treatment of solid tumors; and small molecule targeted drugs for the treatment of KRAS G12C/G12D mutations.

Looking to the future, Dr. Zhu Chenggang said, "Our subsequent series of research and development pipelines will also gradually enter the IND declaration stage. Forward Pharma will continue to focus on the targeted therapy field of cancer, deeply explore unmet clinical needs, and provide targeted drug solutions specifically for them to provide clinical benefits to a wide range of cancer patients."