IL-34

Tumor-associated macrophages (TAMs) can inhibit tumor immune efficacy. Colony stimulating factor 1 receptor (CSF-1R)/CSF-1 pathway involved in regulating the function of TAMs. CSF-1R is a tyrosine kinase transmembrane receptor, also a member of the growth factor CSF-1/platelet derived growth factor (PDGF) receptor family.  This receptor family has inherent tyrosine-specific protein kinase activity. CSF-1R participates in the survival, proliferation, differentiation, recruitment, and function of mononuclear phagocytes (such as macrophages, monocytes). IL-34 has biological characteristics similar to CSF-1, but their main differences come from different spatio-temporal regulation. In addition, CSF-1 can function through autocrine and paracrine methods, while IL-34 only works locally.  High levels of CSF-1 have been reported in breast cancer, pancreatic cancer, prostate cancer, ovarian cancer, kidney cancer, and many other types of cancers. Overexpression of CSF-1 and its receptor CSF-1R in tumors is associated with poor prognosis. Therefore, small molecule inhibitors and antibodies against CSF-1R are currently being developed clinically, which show anti-tumor activity. Competitive landscapeAccording to the data from Synapse, there are currently 59 drugs targeting CSF-1R under development, covering 100 different disease areas, with related research institutions reaching 96, and there are 1090 clinical trial results related to CSF-1R-targeted drugs. In addition, the development of CSF-1R-targeted drugs has been supported by 7749 patents, indicating innovation and technological breakthroughs in this field. The research and development of CSF-1R-targeted drugs have also received wide attention and protection, and 4328 related research papers have been published. These papers summarize the important findings in the research and development progress, mechanism research, and clinical application of CSF-1R-targeted drugs. Key DrugAxatilimab Axatilimab (SNDX-6352) is a selective CSF-1R inhibitor developed by Incyte and Syndax Pharmaceuticals, mainly used for the treatment of chronic graft versus host disease (cGVHD)(Phase 3), Idiopathic Pulmonary Fibrosis (Phase 3), and cholangiocarcinoma (Phase 2) among other diseases. CSF-1 has been proven to stimulate the growth and differentiation of donor-derived monocytes into macrophages, thereby stimulating the activation of fibroblasts and the production of collagen proteins, leading to the manifestations observed in various organs of cGVHD patients. The use of axatilimab to block CSF-1R may reduce the number of these inflammatory macrophages and play a crucial role in the treatment of chronic graft versus host disease.  According to results from a phase 1/2 clinical study AGAVE-201, an overall response rate (ORR) of 68% was observed in two dosage groups utilized for further research. A clinically meaningful improvement in symptoms was reported in 53% of patients, as assessed by the Lee Symptom Scale, and 43% of patients continued to receive treatment at the time of data cut-off. The most recent results demonstrated that, out of 40 enrolled patients, the regulatory authority approved endpoint ORR reached 82%, and 58% of patients reported a significant improvement in cGVHD-related symptoms using the Lee Symptom Scale. Emactuzumab  Emactuzumab (RG-7155) is a CSF-1R inhibitor developed collaboratively by Roche and Celleron Therapeutics and is primarily used to treat tenosynovial giant cell tumor (Phase 3), ovarian cancer (phase 2), and peritoneal malignant tumors (phase 2) among others. As a leading therapeutic antibody against CSF-1R, emactuzumab functions by targeting and eliminating tumor-associated macrophages (TAMs). The drug has shown high safety in patients and significant efficacy on diffuse Tenosynovial giant cell tumor (TGCT), a rare disease characterized by the abnormal proliferation of macrophages in the synovial tissue of joints and tendons. According to a clinical study conducted on patients with diffuse TGCT, the overall response rate of Emactuzumab was 71% (45/63), and the disease control rate was 98% (62/63). In 1-year and 2-year follow-up, MRI scans showed that 19/27 (70%) and 9/14 (64%) of patients respectively continued to respond to the treatment, indicating that Emactuzumab has a long-lasting effectiveness. Mechanism of action of Emactuzumab In contrast to the early approved CSF-1R multi-target inhibitors like Surufatinib, Pexidartinib, Vorolanib, etc., the new generation CSF-1R inhibitors have a better selectivity. They can significantly reduce the side effects of off-target effects and show good efficacy in clinical trials. The development of small molecule drugs has further enhanced patient's oral convenience, such as Pimicotinib from Handi Pharmaceuticals. In addition to playing a crucial role in the field of anti-cancer treatments, CSF-1R inhibitors also have wide application prospects in many areas including inflammation-related diseases and skeletal-related diseases. In these indications, the application prospect of CSF-1R inhibitors will be further expanded and explored. Through continuous exploration and innovation, CSF-1R inhibitors are expected to become an important therapeutic choice in multiple fields, bringing more hope and well-being to patients.

REDWOOD CITY, Calif., Jan. 30, 2023 (GLOBE NEWSWIRE) -- AmMax Bio, Inc. (“AmMax”), a private clinical-stage biopharmaceutical company developing innovative therapeutics in oncology, including a next-generation antibody-drug conjugate (ADC) and a mAb targeting colony-stimulating factor 1 receptor (CSF1R), today announced that the first patients have been dosed in the Company’s Phase 2b study evaluating AMB-05X for the treatment of tenosynovial giant cell tumor (TGCT). The AmMax phase 2b trial is an open-label, adaptive, dose-ranging study to evaluate the safety, efficacy and pharmacokinetics of intra-articular administration of AMB-05X in patients with TGCT after 24 weeks of treatment and an additional long-term extension period. (ClinicalTrials.gov Identifier: NCT05349643) “The expansion of our TGCT program into this Phase 2b study builds on the strong proof-of-concept safety and efficacy data reported in 2022 which evaluated the treatment of AMB-05X in TGCT patients over a 12-week period,” said Larry Hsu, Ph.D., Chief Executive Officer of AmMax Bio. “Since announcing those results, both FDA Fast Track designation and EMA PRIME designation have been granted to AMB-05X, reflecting its significant potential to address the unmet medical need for this patient population with few treatment options. With six months of treatment, we believe patients will receive greater benefit with AMB-05X than any other pharmacological options, and we plan to use the data from this trial to finalize our Phase 3 study design.” “Encouraged by the treatment experience with AMB-05X from the earlier POC study, our patients are excited to enroll in this Phase 2b trial,” stated the principal investigators, Hans Gelderblom, M.D., Ph.D., Chair of Medical Oncology, and Michiel van de Sande, M.D., Professor of Orthopedic Oncology at the Leiden University Medical Center in the Netherlands. “With AMB-05X already demonstrating positive safety and efficacy over a 12-week treatment period, this larger Phase 2b study, with a broader enrollment scope, will assess the treatment durability of this novel, locally administered therapy over a 24-week treatment period. If successful, AMB-05X would provide TGCT patients with a much-needed alternative to immediate surgical resection and the associated complications, long recovery times, and high rates of recurrence.” About TGCT Tenosynovial Giant Cell Tumor (TGCT), with a worldwide incidence of over 300,000, is a serious and debilitating locally aggressive tumor in which patients can experience severe pain, disability, and diminished quality of life. Surgical resection, the primary standard of care for TGCT, carries significant risk to patients, including complications from infections and prolonged postoperative care, and frequent relapse. A safe and efficacious pharmacologic therapy that can be used as an alternative to surgery remains a significant unmet need. AmMax is uniquely positioned to address this need for patients with TGCT by leveraging the target selectivity and enhanced safety profile of AMB-05X via local intra-articular administration, while creating a sizable commercial opportunity from improved patient care. About AMB-05X A potent monoclonal antibody against CSF1R granted Fast Track designation by the FDA and PRIME designation by EMA for TGCT, AMB-05X represents a therapeutic platform targeting serious macrophage-driven inflammatory, fibrotic and neovascular diseases. CSF1R, via its binding to two regulatory cytokines, CSF1 and IL-34, is critically involved in the regulation of macrophages and related cells in multiple biological processes across many organ systems, making it an attractive target with broad therapeutic applications. About AmMax Bio Inc. ​AmMax is a private biotechnology company focused on leveraging our core expertise in translational science and drug development to build a clinical portfolio of first-in-class and best-in-class oncology products in areas of significant unmet medical need. The Company’s core portfolio consists of AMB-101, a novel antibody-drug conjugate (ADC) with a proprietary next generation topoisomerase 1 inhibitor-based linker-payload that is expected to enter the clinic in 2023, and AMB-05X from the Company’s CSF1R platform as a potentially best-in-class locally administered treatment for TGCT. AmMax is currently leveraging positive clinical data and an improved safety profile to advance AMB-05X in an actively enrolling Phase 2 study.

AMB-05X is the First and Only Investigational Drug Candidate to Receive PRIME Designation for the Treatment of TGCT PRIME Designation Validates Unique Therapeutic Potential of AMB-05X as Demonstrated in Prior Phase 2 Study of TGCT Initial Results from Phase 2b Trial Remains on Track for Second Half of 2023 REDWOOD CITY, Calif., Jan. 19, 2023 (GLOBE NEWSWIRE) -- AmMax Bio, Inc. (“AmMax”), a private clinical-stage biopharmaceutical company developing innovative therapeutics in oncology, including a next-generation antibody-drug conjugate (ADC) and a mAb targeting colony-stimulating factor 1 receptor (CSF1R), today announced that the European Medicine Agency (EMA) has granted AMB-05X Priority Medicines (PRIME) designation for the treatment of tenosynovial giant cell tumor (TGCT). “The positive proof-of-concept data from our prior 12-week Phase 2 study of AMB-05X in TGCT provided the basis for our PRIME application,” said Larry Hsu, Ph.D., Chief Executive Officer of AmMax Bio. “We appreciate EMA’s decision to award AMB-05X its PRIME designation, which validates the high potential therapeutic value of the program and the significant unmet medical need for patients impacted by TGCT.” In November 2022, AmMax presented positive Phase 2 data for the novel local administration of AMB-05X in patients with TGCT at the Connective Tissue Oncology Society (CTOS) meeting. The significant efficacy data across multiple clinical endpoints and a favorable safety pro the potential of AMB-05X as a best-in-class therapy for the treatment of TGCT, regardless of surgical resectability. PRIME designation was launched by the EMA to enhance support for the development of medicines that target an unmet medical need. PRIME fosters the efficient development of medicines by enhancing interaction and early dialogue with developers of promising medicines, to optimize development plans and speed up evaluation so these medicines can reach patients earlier. Through PRIME, the EMA offers early and proactive support to medicine developers to optimize the generation of robust data on a medicine's benefits and risks and enable accelerated assessment of medicines applications. This will help patients to benefit as early as possible from therapies that may significantly improve their quality of life.1 In September 2022, AMB-05X was also granted Fast Track designation by the U.S. Food and Drug Administration (FDA). 1 About TGCT Tenosynovial Giant Cell Tumor (TGCT), with a worldwide incidence of over 300,000, is a serious and debilitating locally aggressive tumor in which patients can experience severe pain, disability, and diminished quality of life. Surgical resection, the primary standard of care for TGCT, carries significant risk to patients, including complications from infections and prolonged postoperative care, and frequent relapse. A safe and efficacious pharmacological therapy that can be used alongside surgery remains a significant unmet need. AmMax is uniquely positioned to address this need for patients with TGCT by leveraging the target selectivity and enhanced safety pro AMB-05X via local intra-articular administration, while creating a sizable commercial opportunity from improved patient care. About AMB-05X A potent monoclonal antibody against CSF1R granted Fast Track designation by the FDA and PRIME designation by EMA for TGCT, AMB-05X represents a therapeutic platform targeting serious macrophage-driven inflammatory, fibrotic and neovascular diseases. CSF1R, via its binding to two regulatory cytokines, CSF1 and IL-34, is critically involved in the regulation of macrophages and related cells in multiple biological processes across many organ systems, making it an attractive target with broad therapeutic applications. About AmMax Bio Inc. ​AmMax is a private biotechnology company focused on leveraging our core expertise in translational science and drug development to build a clinical portfolio of first-in-class and best-in-class oncology products in areas of significant unmet medical need. The Company’s core portfolio is a novel antibody-drug conjugate (ADC) with a proprietary next generation topoisomerase 1 inhibitor-based linker-payload (the TMALIN platform) that is expected to enter the clinic in 2023. Additionally, the Company’s CSF1R platform includes AMB-05X, a potentially best-in-class locally administered treatment for TGCT. AmMax is currently leveraging positive clinical data and an improved safety pro advance AMB-05X in an actively enrolling Phase 2 study. For more information, please visit the company’s website at . Contact AmMax Bio, Inc. Andrew Sauter, CFO Email: andrewsauter@ammaxbio.com Tel: 650-787-3777