Self-developed solid tumor and the first innovative drug for immune diseases, Amerifi Bio won 6 INDs in half a year

2021 was an unusual year for Amerifi Biologics, with the company winning ind for six clinical indications in the United States and China in August and December 2021, achieving its first clinical milestone since its founding.

Among the 6 IND approvals, 5 of them are from the IPG1094 pipeline independently developed by Emeder Biologics, which is the world's first small molecule inhibitor targeting macrophage movement inhibitor (MIF), and the company is conducting clinical trials for five indications of multiple myeloma, solid tumor, multiple sclerosis, systemic lupus erythematosus, and psoriasis in Australia, the United States, and China.

In addition to IPG1094, the other is IPG7236, which is the first CCR8 antagonist in China to enter the clinic for the treatment of a variety of solid tumors, and is currently approved by the US FDA and china CDE, and is also carrying out clinical trials in China and the United States.

In addition to the first echelon of IPG1094 and IPG7236, Amerifi Bio has more than ten new drugs in the second, third, fourth and fifth echelons of clinical pipeline layout, all of which are First-in-Class innovative drugs independently developed by the company. Arterial Network interviewed Dr. Fan Guohuang, the founder of Emmephi Biologics, to understand the company's development history, core products, competitive advantages and future plans.

GSK core expert formation,

Deep ploughing of tumors and degenerative diseases for 28 years

Amerifi Bio, nanjing Amerifi Biopharma Technology Co., Ltd., founded in 2016, is a biopharmaceutical company focusing on the research and development of innovative drugs for the treatment of malignant tumors, autoimmune and neurodegenerative diseases, the company to immunomodulatory and other links to carry out new drug research and development, has formed 15 new drug research and development pipelines, rare in China.

With 28 years of pharmacological research experience in major diseases such as malignant tumors and neurodegenerative lesions, Dr. Fan Guohuang, founder of Emmefa Biologics, managed the new drug R&D team at GSK's China R&D Center for 6 years, and led preclinical research and clinical trials of new drugs in a number of major disease areas. Before joining GSK, Dr. Fan Guohuang was a tenured professor at a well-known university in the United States, published more than 60 research papers in important international journals, obtained more than 20 invention patents, and won many honors such as the National Natural Science Award.

Dr. Wang Jianfei, Chief Scientific Officer (CSO) of the Company, also previously worked at GSK, and was the Director of the Integrated Biotechnology Research Department of the GSK China R&D Center, which established a complete preclinical R&D platform, provided target verification, pilot compound optimization, pharmacodynamic and pharmacokinetic technical support for dozens of projects of the company, and won many commendations from the GSK China R&D Center, including the Gold Award. As the leader of GSK's global integrated biological platform, Dr. Wang Jianfei has successfully promoted a number of new drug research and development projects to complete clinical declarations and enter clinical trials, and was named Senior GSK Fellow (the company's highest level of scientific research scholar).

Dr. Wang Jianfei has more than 28 years of experience in translational medicine research, publishing more than 70 papers in world-renowned international journals and obtaining a number of patents.

In addition to the company's founder and chief scientific officer, Amerifi Bio has brought together a large number of outstanding experts in the fields of medicine, pharmacology, medicinal chemistry, biology and other fields, and the team members are from the core R&D management and practice positions of large multinational pharmaceutical companies such as GSK and Pfizer, as well as famous universities and scientific research institutions at home and abroad, participating in dozens of new drug projects at the preclinical and clinical stages.

Development of new drugs based on "immune imbalance",

Small molecule antagonists have excellent safety profile

Macrophage mobility inhibitor (MIF) is the only cytokine with enzymatic activity that promotes tumor cell proliferation by acting on the tumor suppressor gene p53, and myeloid-derived suppressive cell formation (MDSC) through tumor exosomes, inhibiting the proliferation of CD8+ T cells and their anti-tumor function.

Because of its anti-tumor properties, MANY companies have developed antibody drugs for MIF, but most clinical studies have fallen in the second phase of clinical practice. Dr. Fan Guohuang, founder of Emmephi Biology, explained the possible reasons: "MIF is different from other cytokines, it is present in the exosome structure, there is no signal peptide, and it is always wrapped in the structure of the cell membrane, so it is difficult for antibody drugs to act on the target on the cell membrane." ”

The new drug development strategy of Amerifi Biologics is to develop a miF small molecule inhibitor that can pass through the cell membrane for the tautomerase activity of MIF, and at present, there is no small molecule inhibitor for MIF on the market worldwide. MIF inhibitors can not only directly inhibit the growth of tumor cells, but also reverse the tumor immunosuppressive microenvironment by inhibiting MDSC production, with dual anti-tumor functions.

In addition, in the development of autoimmune diseases, abnormally high-expression MIF promotes the continuous polarization of macrophages to M1 type by inhibiting p53 and other pathways, resulting in amplification of inflammation and tissue and organ damage. MIF inhibitors promote the transition from M1 type macrophages (inflammatory) to M2 type (anti-inflammatory), re-establish immune balance, and fundamentally treat disease.

According to the preclinical study of AmeriFi Biologics, IPG1094 shows extremely high safety, with a safety window greater than 40 times, and rare without significant toxic side effects.

CCR8 is a chemokine receptor that is expressed both in most solid tumors and highly on tumor-associated regulatory T cells (Treg), with very low or no expression on non-tumor-associated Tregs. Previously, there have also been biopharmaceutical companies to develop CCR8 antibody drugs, but because CCR8 is not only expressed on Treg, but also on memory CD4 lymphocytes, NK cells, bladder epithelial cells and other cells, if you rely on the ADCC effect of the Fc end of the antibody anti-cancer, then it will also produce non-specific killing of these normal cells, causing serious immunotoxic side effects.

For CCR8, Emeril Bio also adopted an antagonist regimen. Dr. Fan Guohuang, founder of Emmephi Biologics, introduced: IPG7236 inhibits Treg's infiltration and expansion in the tumor by blocking CCR8-mediated signaling, as well as Treg's immunosuppressiveness of effector T cells. Since this pathway does not kill CCR8-expressing tumor cells through ADCC, but only blocks the CCR8-mediated signaling pathway, and ultimately inhibits the migration, multiplication, and immunosuppressive properties of tumor-related Tregs with high CCR8 expression, it can effectively avoid the toxic side effects caused by ADCC.

Recently, Amerifi Biologics' CCR8 antagonist IPG7236 has completed the first case of subject administration in the United States, and no drug-related adverse reactions have been seen.

It is reported that Emmefay Bio has another 4 drug research pipelines in the second echelon and is currently declaring IND; there are 3 third echelon pipelines that are screening candidate molecules; the fourth echelon drugs have started drug screening; and the fifth echelon drugs are undergoing target research and verification. The company will also complete the B1 round of financing in the near future, and the funds raised will support the construction of the company's overseas branches and promote the company's clinical pipeline into the second phase.