EGFRvIII

CHARLOTTE, NC, USA I September 04, 2024 I Adaptin Bio , a biotechnology company focused on developing precision cancer therapies with improved delivery to the brain and other tissues, has emerged from stealth today with the announcement that FDA has cleared an Investigational New Drug (IND) application for its APTN-101 program in glioblastoma (GBM), the most common and aggressive primary brain tumor. The clearance will enable the initiation of a first-in-human Phase 1 clinical trial to evaluate this investigational candidate in GBM. APTN-101 is a proprietary BRiTE (Brain Bispecific T cell Engager) therapeutic designed to target EGFRvIII, a specific protein linked to aggressive brain tumors. In preclinical studies, APTN-101 has shown a greater than 7-fold increase in distribution into the brain, with significant potential in eradicating malignant glioma tumors as a potentially best-in-class therapy. The Phase 1 clinical trial will assess the safety and efficacy of APTN-101 in patients diagnosed with WHO Grade IV Malignant Glioma, also known as GBM. Current treatment options for GBM include surgery, radiotherapy, and chemotherapy, which aim to remove or destroy tumor cells within the brain but fail to completely eliminate the disease due to its invasive nature. GBM deeply infiltrates the brain and despite aggressive treatment, residual tumor cells often lead to disease recurrence. GBM represents one of the most aggressive and challenging forms of brain cancer, with a median survival rate of just 12-18 months post-diagnosis, with only 5% of patients surviving beyond five years. The disease accounts for approximately 15,000 new cases per year in the US. Secondary malignant brain tumors account for about 200,000 new cases annually. This critical unmet need demands innovative therapies that can overcome the limitations of current treatments that do not cross the blood brain barrier. “The FDA clearance is a significant achievement for our collaboration with Adaptin. Based on results from preclinical models in orthotopic malignant glioma, we are excited to begin this clinical trial to evaluate the safety and efficacy of APTN-101,” said Mustafa Khasraw, M.D., Professor of Neurosurgery, Medicine, Integrative Immunobiology, Cancer Biology and Pharmacology at Duke University. “APTN-101’s ability to cross the blood-brain barrier and target glioma cells directly offers a promising new approach.” “We’re thrilled to initiate clinical trials with APTN-101 following FDA clearance of our first-in-human trial,” said Michael J. Roberts, Ph.D., CEO, Adaptin Bio. “Our proprietary BRiTE technology harnesses the immune system’s remarkable ability to target and deliver therapeutics to specific tissues, including the brain, potentially revolutionizing treatment for difficult-to-treat cancers. APTN-101 validates the BRiTE platform and its ability to enhance transfer of therapeutics into the brain. We are committed to advancing this novel therapy as a new potential therapy for glioblastoma patients who desperately need new therapies.” “Adaptin’s innovative delivery technology has the potential to revolutionize treatment for cancer and central nervous system disorders. We are proud to support Adaptin Bio as part of our ongoing commitment to partnering with visionary entrepreneurs and translating groundbreaking technologies from leading academic institutions into impactful solutions,” said James Ahern, Managing Partner of Laidlaw & Company and Founding Partner of Lucius Partners, who is an investor in Adaptin Bio. In preclinical studies, APTN-101 has shown impressive efficacy in eliminating malignant glioma tumors across various aggressive orthotopic models. The BRiTE platform, developed by researchers in the Department of Neurosurgery at Duke University under the leadership of Dr. John H. Sampson, harnesses the ability of T cells to precisely target and destroy glioma cells while effectively navigating the brain’s unique environment. Adaptin Bio’s proprietary BRiTE technology leverages the enhanced “hitchhiking” capabilities of manipulated immune cells to deliver therapeutic agents directly to brain tumors. This innovative approach has demonstrated high specificity for EGFRvIII expressing glioma cells, dose-responsive efficacy against diverse patient-derived glioma cell lines, and a favorable safety profile. Additional BRiTE targets are being evaluated. By manipulating the immune system either in vivo or ex vivo, BRiTE aims to overcome traditional treatment barriers and offer a promising new therapeutic option for patients with intracerebral malignancies. About Adaptin Bio Adaptin Bio is a biotechnology company developing novel therapies for oncology and central nervous system disorders with improved drug delivery to the brain and other tissues. The company’s proprietary Brain Bispecific T cell Engager (BRiTE) technology was developed by researchers at the Department of Neurosurgery at Duke University. The company’s mission is to develop novel therapies to improve patient outcomes in difficult-to-treat cancers. For more information, visit www.adaptinbio.com . SOURCE: Adaptin Bio

Adaptin Bio is launching with plans to bring a bispecific T cell engager for glioblastoma, a deadly form of brain cancer, into the clinic. The company received FDA clearance to start its clinical trial, which will be run at Duke University and enroll around 25 patients. The bispecific T cell engager was developed by researchers led by John Sampson, who previously was chair of the neurosurgery department at Duke and is now dean of the University of Colorado’s School of Medicine. Duke’s work on the therapy was supported by a $5 million NIH grant, and Adaptin conducted preclinical work on the asset with funds from an undisclosed pre-seed round. Adaptin is closing its seed round this week, but declined to disclose the amount. The company is led by Michael Roberts, who previously was VP of business development at Chelsea Therapeutics, which Lundbeck acquired in 2014. The drug, called APTN-101, is designed to bring T cells to cancer cells in hopes of stoking the immune system into fighting the cancer. The therapy targets both EGFRvIII, a protein overexpressed in glioblastoma, as well as CD3, which is found on T cells. Amgen and Roche had developed EGFRvIIIxCD3 bispecific antibodies, but both stopped work on their assets. Roche announced in February it was axing its glioblastoma bispecific amid broader pipeline cuts across its portfolio . “There has been no progress for the last 20 years — zero,” said Mustafa Khasraw, a neurosurgery professor who took over the project at Duke after Sampson moved to Colorado. He noted that there are several key obstacles, ranging from the methods used to develop drugs to the challenge of getting several biopsies to the blood-brain barrier. Khasraw and others have begun testing potential therapies for brain cancers in different ways, including first testing them on biopsies before deciding whether to administer them in humans. GSK said in May it was planning a Phase 3 trial of Zejula in glioblastoma based on the results of a combined Phase 0/2 study that used that approach. A key test for Adaptin Bio will come down the line. The startup plans to combine its bispecific T cell engager with cell therapy, and take advantage of a concept called “hitchhiking,” where manipulated T cells can move past the blood-brain barrier, hopefully directing more of the T cell engagers to the brain cancer. “We have a technology that circumvents and overcomes some of the key limitations when we talk about delivering treatments to the brain, even T cells into the brain,” Roberts said. “I do think it’s the delivery aspect that really makes the difference here.” “We need to do more innovative trials — thinking outside the box and using new approaches — because all the traditional approaches have failed in this disease for at least two decades,” Khasraw said.

DAEJEON, South Korea, July 8, 2024. PharmAbcine Inc., a clinical-stage biotech company focusing on next-generation antibody therapeutics, announced that PMC-309, VISTA-targeting immuno-oncology program, received safety approval for the first dose cohort (0.2mg/kg) in Phase 1a/b clinical trial for patients with advanced or metastatic solid tumors in Australia. The second dose cohort (0.5mg/kg) is currently ongoing. The first dose cohort (0.2mg/kg) of PMC-309 was initially administered in January 2024 and received safety approval in April 2024. Currently, the second dose cohort (0.5mg/kg) has been administered to two patients, with the third patient scheduled to receive treatment soon. PMC-309 is an IgG1 monoclonal antibody specifically binding to VISTA on immunosuppressive cells, demonstrating excellent binding affinity at various pH conditions within the tumor microenvironment (TME). By inhibiting VISTA, PMC-309 offers a differentiated mechanism of action, contributing to anti-cancer effects through the activation of T cells, monocytes, and the proliferation of M1 macrophages. This open-label Phase 1a/b clinical trial involves a total of 67 patients and comprises two phases: Phase 1a and Phase 1b. Phase 1a includes PMC-309 monotherapy and combination therapy with KEYTRUDA (pembrolizumab) to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). Phase 1b will evaluate the safety and tolerability of PMC-309 monotherapy and combination therapy with KEYTRUDA at the RP2D. The clinical trial is being conducted at four institutions in Australia. Dr. Jin-San Yoo, Chief Executive Officer of PharmAbcine Australia Pty, the Australian subsidiary of PharmAbcine Inc., stated, "It has been 10 years since the first generation of immuno-oncology drugs entered the market. During this time, these drugs have been administered to numerous cancer patients. While some patients have benefited, many have developed resistance, and others have passed away. The need for next-generation immuno-oncology drugs is critical. The confirmation of the safety of the first dose cohort of PMC-309 is just the beginning of this trial. We look forward to gradually verifying the safety and efficacy of PMC-309 through the planned higher dose cohorts. We are also preparing for the combination trial of PMC-309 with KEYTRUDA in collaboration with MSD without any delays." He added, "We are committed to providing new treatment options to patients suffering from the limitations of first-generation immuno-oncology drugs." For more information on the clinical trial, please visit clinicaltrials.gov, identifier NCT05957081. KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About PharmAbcine Inc. PharmAbcine is a clinical stage public company developing next generation IgG based therapeutics to treat cancer, neovascular eye diseases, and vascular related unmet needs. The Company's main pipeline include clinical assets olinvacimab, PMC-403, and PMC-309. Olinvacimab, the Company's lead asset, is ongoing a Phase 2 trial in combination with MSD's pembrolizumab for mTNBC patients in Australia to reconfirm the encouraging result from Phase 1b olinvacimab plus pembrolizumab trial, delivering 50% ORR, 67% DCR, and clean safety profile. PMC-403 is a novel TIE2-activating antibody that stabilizes dysfunctional leaky disorganized pathological vessels and can be used for vascular-related eye disease, including wet AMD (Age-related Macular Degeneration). PMC-403 is currently undergoing Phase 1 trial for neovascular AMD patients in Korea. PMC-403 is also being explored to expand into wider therapeutic areas related to pathological vessels including vessel-related rare diseases and non-rare diseases. PMC-309, a novel anti-VISTA-antagonizing IgG in pan pH conditions, is an immune checkpoint regulator that targets MDSC (myeloid derived suppressor cells) and M2 macrophages which play pivotal role in maintaining immunosuppressive TME (Tumor Microenvironment). Phase 1a is ongoing at multicenter in Australia and Phase 1b in combination with MSD's pembrolizumab PMC-309 + Pembrolizumab combo is in plan. PMC-005, is an anti-EGFRviii IgG that only binds to EGFRviii expressed on cancer cells and can be applied to various modalities including CAR-T, CAR-NK, CAR-Macrophage, T cell/NK cell engager, and Radio-Immunotherapy. SOURCE PharmAbcine Keytruda (pembrolizumab) FDA Approval History Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.