PTP1B

FARMINGDALE, N.Y., Oct. 02, 2024 (GLOBE NEWSWIRE) -- DepYmed, Inc. (“DepYmed” or the “Company”) is a clinical-stage pharmaceutical company focused on developing transformative medicines for many poorly treated diseases that may benefit significantly by targeting the protein tyrosine phosphatase (PTP) family of enzymes. Today, DepYmed announces co-founder and research advisor Nicholas Tonks, Ph.D. will present data at the 9th World Rett Syndrome Congress in Queensland, Australia being held October 2-5, 2024. Dr. Tonks’ presentation, titled, “PTP1B inhibition – a clinic-ready, mechanism-based approach to the treatment of Rett syndrome” will occur on October 3, 2024 at 4:30PM local time. In the presentation, Dr. Tonks discusses the nature of Rett syndrome as an X-linked neurological disorder caused primarily by mutations in a transcriptional regulator, methyl CpG binding protein 2 (MECP2). He then outlines the preclinical work completed for the Company’s PTP1B inhibitor, DPM-1003, which improved a wide range of Rett syndrome phenotypes in RTT mice. He concludes that these data provide validation of PTP1B as a mechanism-based, therapeutic target for Rett syndrome, suggesting DPM-1003 as a new approach to therapeutic intervention in the disease. DPM-1003 is currently poised to enter clinical development and has been cleared by the FDA for clinical testing in the United States under an IND. At this time, the Company is actively raising funds to support this clinical initiative. The 9th World Rett Syndrome Congress includes the latest in research, clinical innovations, and drugs. Seminars will be presented by world-renowned experts in Rett syndrome. The Conference is hosted by the Rett Syndrome Association of Australia, a not-for-profit organization managed by a committee of volunteers most of whom are parents of Rett syndrome children. The Association seeks to enhance the quality of life for persons with the syndrome and their families, and to be of assistance to anyone interested in the disorder. About DPM-1003 Protein tyrosine phosphatases are major players in the control of cell signaling pathways that are disrupted in many diseases, yet to date no drug modulators of these enzymes have been successfully developed. DepYmed is the first company to develop a new class of orally bioavailable drug candidates that act by allosterically inhibiting PTP1B, one of the most important PTP drug targets. One of its lead compounds has shown promising efficacy in preclinical models of Rett syndrome, and the Company hopes to initiate a phase 1 clinical trial in 2024. DPM-1003 has been granted Orphan Drug designation by the U.S. Food and Drug Administration and conditionally designated under the FDA’s Rare Pediatric Disease program. About Rett Syndrome Rett syndrome is a progressive neurodevelopmental disorder that almost exclusively affects females. Infants with Rett syndrome generally develop normally for 6 to 18 months after birth. At this point, they lose previously acquired skills (developmental regression) such as purposeful hand movements and the ability to communicate. Affected children often develop autistic-like behaviors, breathing irregularities, feeding and swallowing difficulties, growth retardation, and seizures. Most Rett syndrome cases are caused by mutations of the MECP2 gene on the X chromosome and can present with a wide range of disability ranging from mild to severe. The expression of PTP1B, DepYmed’s target in Rett syndrome, is regulated by MECP2; in turn, PTP1B controls important cell functions that are disrupted in the disease. About DepYmed, Inc. DepYmed Inc., is a New York based rare disease and cancer therapeutic development company that was founded to capitalize on the scientific discoveries of the Tonks lab at Cold Spring Harbor Laboratory in the physiological function of PTP1B and ways to modulate its role in various human diseases. DepYmed is currently developing a new class of potent, orally bioavailable small molecule allosteric inhibitors of the enzyme PTP1B as novel therapeutics for Rett Syndrome, different types of cancer, metabolic diseases, obesity, and Alzheimer’s Disease where the PTP1B target has shown promise. In addition, DepYmed has also discovered a novel class of small molecules with copper chelating properties that it is developing as potential therapeutic agents for diseases such as Wilson disease and various cancers. The company is actively developing a deep pipeline of new compounds with broad therapeutic potential in these emerging drug classes in collaboration with Cold Spring Harbor Laboratory. For more information, please visit the Company’s website at: www.depymed.com. For Media Inquiries please contact: Jules AbrahamJQA Partners, Inc.jabraham@jqapartners.com 917-885-7378 DepYmed:info@depymedinc.com

On July 29, Boehringer Ingelheim announced a major acquisition, with plans to buy Nerio Therapeutics for $1.3 billion. Nerio Therapeutics, a pharmaceutical company focused on phosphatase research, has successfully developed highly selective phosphatase PTPN2/N1 inhibitors for an innovative regimen of tumor immunotherapy. With a leading position in the global oncology market, Boehringer Ingelheim has continuously strengthened its strategic presence in oncology in recent years. According to preliminary statistics, the company has established cooperative relationships with a number of well-known pharmaceutical companies in recent years to accelerate the construction of tumor research and development pipelines: In December 2020, Boehringer Ingelheim acquired NBE Therapeutics for 1.18 billion euros to acquire novel antibody-coupled drugs to address the challenge of refractory solid tumors. In the same month, Boehringer Ingelheim acquired Labor Dr. Merk & Kollegen to increase its research and development and clinical manufacturing capabilities to support its next generation cancer immune drug development program. In January 2021, the company entered into a strategic partnership with Enara Bio to develop innovative cancer immunotherapies using its Dark Antigen™ platform. In September 2021, Boehringer Ingelheim acquired Abexxa Biologics to gain expertise in targeting cancer-specific proteins within cells, expanding the range of potential cancer antigen targets. In June 2022, the company entered into A global licensing agreement with the Agency for Science, Technology and Research of Singapore (A*STAR) to acquire the development and commercialization rights for A*STAR's series of innovative tumor-specific antibodies. In January 2023, Boehringer Ingelheim and 3T Biosciences entered into a strategic collaboration and licensing agreement to jointly explore and develop the next generation of cancer therapies. In March 2023, the company partnered with Covant Therapeutics to develop a covalent drug candidate for the ADAR1 cancer target. In November 2023, Boehringer Ingelheim acquired T3 Pharmaceuticals for CHF 450 million (approximately $508 million), which specializes in innovative therapeutic platforms that enhance immunotherapy with live bacteria. In the same month, Boehringer Ingelheim established a strategic collaboration and licensing agreement with Phenomic AI to jointly discover key targets in rich stromal cancers. In February 2024, Boehringer Ingelheim and CBmed entered into a long-term strategic partnership to accelerate the development of first-of-its-kind oncology drugs using translational medicine to improve the lives of patients. In May 2024, Boehringer Ingelheim and OSE expanded their collaboration to jointly develop first-of-its-kind therapies for tumor and cardio-renal metabolic diseases, including the anti-SIRRP α tumor Immunity program and the cis targeted anti-PD1 / cytokine platform. While Boehringer Ingelheim does not yet have a significant oncology product in the market, its oncology pipeline includes several promising candidates, such as Zongertinib(Phase 1), Brigimadlin (Phase two-thirds) and BI-764532 (Phase 2). Zongertinib is an innovative covalently bound, orally effective and selective HER2 small molecule inhibitor. It covalently binds to the tyrosine kinase domain (TKD) of both wild-type and mutant HER2 receptors, including exon 20 mutations, while preserving the wild-type signal of EGFR, thereby demonstrating good tolerability and safety while ensuring efficacy. Data from the Phase 1a/1b clinical study of Zongertinib monotherapy for HER2-variant advanced solid tumors (NCT04886804), presented at the ASCO meeting in 2024, showed that Zongertinib demonstrated superior efficacy and was well tolerated in patients with HER2-mutation-positive advanced NSCLC. Brigimadlin is a mouse dual microhomologous gene 2 (MDM2) -p53 antagonist targeting MDM2-amplified tumors such as biliary adenocarcinoma, non-small cell lung cancer, and pancreatic cancer. Currently, Brigimadlin's first-line treatment of dedifferentiated liposarcoma (DDLPS) has entered phase 2/3 of clinical trials. New results from the Phase 1a/1b study (NCT03449381) presented at the ASCO Meeting in 2024 show that Brigimadlin induces proteomic changes in DDLPS that may serve as potential biomarkers for predicting treatment response and adverse events. BI 764532 is a first-in-class T cell-mediated bisspecific antibody developed at Boehringer Ingelheim that induces a patient's own T cells to attack cancer cells expressing DLL3. BI 764532 has received fast track approval from the FDA for the treatment of advanced SCLC and advanced or metastatic extrapulmonary neuroendocrine carcinoma. In both DLL3-positive cell and xenograft models, BI 764532 showed potential preclinical antitumor activity. PTPN2 and PTPN1 (also known as PTP-1B) are phosphatases that negatively regulate multiple cytokine signaling pathways and T cell receptor (TCR) signaling pathways. They inhibit inflammation by dephosphorylation of JAK and STAT family members, and reduce T-cell sensitivity to antigens by phosphorylation of LCK and FYN. PTPN2 deletion was found to increase the number of activated cytotoxic CD8+T cells in the tumor, improve antigen presentation and sensitivity to IFNγ, and thus enhance tumor sensitivity to CD8+T cells. Given the critical role of PTPN2/N1 in tumor and immune cells and its highly conserved active sites, researchers are developing PTPN2/N1 inhibitors. Currently, there are several PTPN2/N1 inhibitors, such as ABBV-CLS-579 and ABBV-CLS-484 (AC484). AC484 is an oral PTPN2/N1 active site inhibitor that enhances the response to interferon and promotes the activation and function of immune cell subsets. In a PD-1-resistant mouse model, AC484 monotherapy showed significant antitumor effects. Currently, a Phase 1 clinical trial of AC484 is underway to evaluate its efficacy alone or in combination with PD-1 inhibitors or VEGFR tyrosine kinase inhibitors (TKI) in the treatment of advanced or metastatic solid tumors. In addition, using Chemistry42, its generating-AI platform, Insili has also developed a novel PTPN2/N1 inhibitor that has drug-like properties, good oral bioavailability in vivo, and strong in vivo anti-tumor activity, demonstrating nanoscale inhibitory efficacy.

Boehringer Ingelheim has acquired California biotech Nerio Therapeutics, picking up a preclinical novel immune checkpoint inhibitor in what the drugmaker is calling a "significant step" for its immuno-oncology pipeline. In a deal that Boehringer says is worth a total of $1.3 billion, the German drugmaker will secure the rights to Nerio’s small molecules, which inhibit the protein tyrosine phosphatases N1 and N2 (PTPN1 and PTPN2), which act as immune checkpoints. Through this mechanism, PTPN1/2 inhibition can activate the immune system to fight cancer cells. According to Boehringer, the company aims to develop the program as a "potential key centerpiece component for its immuno-oncology portfolio" in order to improve cancer patient outcomes. Boehringer Ingelheim laid out bold goals for the company in its 2023 earnings report, shared this past April , aiming for 25 new treatment launches by 2030. Back in June , the drugmaker revealed positive results from a phase 2 trial of survodutide, co-invented with Zealand Pharma, in metabolic dysfunction-associated steatohepatitis (MASH). The drug is being evaluated in five phase 3 trials for obesity, but the partners are betting on it becoming a best-in-class treatment for MASH/NASH.