PTP1B

Boehringer Ingelheim has inked a research collaboration with Tessellate Bio to develop precision medicines for cancers that maintain telomere length to survive and grow. The Amsterdam-based biotech could get more than €500 million ($573 million) in upfront license fees, research funding and milestones, according to a Wednesday release. The partners will focus on advancing oral drugs for ALT (alternative lengthening of telomeres) positive cancers. Telomeres act as protective seals at the end of chromosomes. They get shorter with each round of cell division and eventually reach critically short lengths, causing cells to stop dividing or die, Tessellate CEO Andree Blaukat told Endpoints News in an interview. But ALT positive cancers can keep telomere length, which means the cells continue surviving and dividing. Tessellate said it has discovery-stage candidates that block an unnamed target associated with the “uncontrolled growth” of ALT positive tumor cells. The biotech will now work exclusively with Boehringer on these programs. The candidates trigger DNA damage and cancer cell death while sparing healthy tissue, according to the biotech. The tie-up marks Tessellate’s first partnership with a biopharma company. The biotech previously teamed up with research institutes CMRI and Omico in September 2024 to take a closer look at the prevalence of ALT across tumor types and the genetic influences involved. Around 10% to 15% of all cancers rely on the ALT maintenance mechanism and there’s a “particularly high prevalence” for mesenchymal tumors and brain cancers, Blaukat said. More common cancers — such as breast, colorectal and lung — are ALT positive in the range of 5% or less, he added. Tessellate is developing a companion diagnostic device to help identify patients with more common cancers who may benefit from a treatment that addresses the ALT mechanism. Elsewhere, the biotech’s lead in-house program targets cancers with loss of function in the retinoblastoma 1 gene, which is responsible for tumor suppression. Tessellate said this feature affects between 80% and 100% of small cell lung cancer cases and more than 40% of triple-negative breast cancer cases. The company emerged from stealth in October 2023 with €8 million in seed funding from BioGeneration Ventures and Forbion. It has labs in Stevenage, UK, alongside its Dutch base. Meanwhile, Boehringer has been bulking up its oncology pipeline in recent years. In July 2024, the German drugmaker bought Nerio Therapeutics in a deal featuring $1.3 billion in biobucks. Nerio is developing small molecule drugs that inhibit PTPN1 and PTPN2. All in all, Boehringer has acquired more than six cancer biotechs since 2019.

First-in-human randomized clinical trial demonstrates safety and tolerability of MD-18, Radella’s novel lead asset from its platform targeting cardiometabolic disease and its adjacencies Company to commence Phase 1b multiple-dose study, furthering clinical development of investigational MD-18 platform NEW YORK, NY, USA I November 07, 2024 I Radella Pharmaceuticals, LLC. , a clinical-stage biopharmaceutical company developing innovative therapies for cardiometabolic disorders, today announced topline results from the Phase 1a MD-18 clinical study evaluating the safety, tolerability, and pharmacokinetics of its investigational MD-18 program for the treatment of obesity and diabetes. MD-18 represents a breakthrough in targeting protein-tyrosine phosphatase 1B (PTP1B), a therapeutic target that has been shown to play a major role in glucose homeostasis and energy metabolism. Radella has identified a family of novel peptides targeting PTP1B through the disruption of a highly-specific, non-allosteric interaction with a second regulatory protein. This approach avoids the off-target effects that have been associated with inhibitors of PTP1B. The Phase 1a study, a single center, single dose, randomized, double-blind, placebo-controlled trial, enrolled 35 healthy subjects who received a single subcutaneous dose of MD-18 ranging from 40mg to 320mg. MD-18 was shown to be safe and well-tolerated across all dose levels, with no serious adverse events or discontinuations. The only treatment-related effects were mild, transient injection site reactions, establishing a favorable safety profile in humans. Notably, subjects receiving MD-18 showed consistent improvements across a number of metabolic parameters after 7 days, including reductions in leptin levels, improved insulin sensitivity, and decreases in alanine aminotransferase (ALT), LDL-cholesterol, and total cholesterol, all of which were not observed in patients on placebo. Patients receiving MD-18 also reported reductions in appetite. “These findings after just a single dose highlight the potential of MD-18 to deliver clinically meaningful metabolic benefits,” said Amir Tirosh, MD, PhD, Chief Medical Officer of Radella and Director, Division of Endocrinology, Diabetes and Metabolism at Sheba Medical Center and Professor of Medicine at Tel-Aviv University School of Medicine. “MD-18’s unique mechanism of action targets both insulin sensitivity and energy expenditure through PTP1B regulation and the leptin pathway, representing a potentially transformative approach for patients with obesity and metabolic disease.” MD-18’s novel approach disrupts a protein-protein interaction (PPI) to regulate PTP1B, a well-validated therapeutic target. Extensive preclinical studies in disease-relevant models have demonstrated that modulation of PTP1B by MD-18 leads to significant improvements in insulin sensitivity and a significant loss of weight and adiposity with preservation of lean muscle mass – crucial differentiators from existing treatments. “Current obesity treatments primarily focus on appetite suppression without addressing the underlying causes of metabolic dysfunction,” said Daniel Cohen, Founder, Chairman, and Chief Executive Officer of Radella. “MD-18’s differentiated mechanism, which has shown promise in improving both insulin sensitivity and additional key metabolic pathways, could potentially offer a new therapeutic option for patients, either as a standalone treatment or in combination with existing therapies. Based on these encouraging Phase 1a results, we look forward to advancing our clinical program to evaluate MD-18’s full therapeutic potential.” Radella plans to initiate a Phase 1b study before the end of the year to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple subcutaneous doses of MD-18 in up to 72 subjects, including overweight volunteers without other health conditions as well as patients with obesity or type 2 diabetes. Cohorts will assess both dose and dose frequency over 4 weeks, with an 8-week extension for the obese and diabetic cohorts. For more information on the MD-18 clinical program, please visit: radellapharma.com . About Radella Pharmaceuticals Radella Pharmaceuticals, LLC., headquartered in New York, NY, with operations in Aberdeen, SCO and Tel Aviv, ISR, is a privately-backed, clinical-stage biopharmaceutical company developing transformative therapies in cardiometabolic disease and beyond. Singularly focused on delivering curative solutions to patients and bettering human health, the company has successfully advanced its lead asset, MD-18, into clinical trials, developing a pipeline of follow-on assets targeting unmet needs in other large therapeutic areas, including neurodegenerative and fatty liver disease. MD-18 is a first-in-class peptide that targets multiple pathways involved in obesity and related metabolic conditions. MD-18 demonstrates a breakthrough in targeting protein-tyrosine phosphatase 1B (PTP1B), a historically challenging therapeutic target that plays a crucial role in metabolic regulation. MD-18’s unique mechanism of action, which targets both insulin sensitivity and energy expenditure through PTP1B regulation and the leptin pathway, represents a potentially transformative approach for patients with cardiometabolic disease and its adjacencies. For more information on Radella’s clinical program and current trials, visit radellapharma.com . SOURCE: Radella Pharmaceuticals

LEXINGTON, Mass.--( BUSINESS WIRE )--Agenus Inc. (“Agenus”) (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, today announced the presentation of new data on two of its promising investigational immunotherapy candidates, botensilimab and AGEN1721, at the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting in Houston, Texas. The data, showcasing potential breakthroughs in treating immune-resistant tumors, will be presented by Dhan Chand, Ph.D., Vice President of Research at Agenus. The first two presentations will spotlight botensilimab, an innovative, investigational, Fc-enhanced anti-CTLA-4 antibody that has shown remarkable efficacy in overcoming immune barriers across several treatment-resistant cancers, including glioblastoma, melanoma, colorectal, pancreatic, and breast cancers. Botensilimab’s unique mechanism of action enhances both innate and adaptive immunity to promote optimal T-cell priming, stimulate antigen-presenting cells, and deplete immune suppressing regulatory T cells in the tumor microenvironment, creating a multi-pronged attack on cold and refractory tumors. “These findings represent a significant milestone in understanding how botensilimab can be optimally combined with both established and emerging therapies,” said Dr. Chand. “What’s particularly compelling is the profound efficacy we’re seeing in traditionally ‘cold’ tumors and treatment-resistant cancers—offering potential new options for patients with limited therapeutic choices.” Featured botensilimab presentations: Preclinical dose-pharmacokinetic-efficacy modeling of botensilimab using a mouse surrogate of the Fc-enhanced anti-CTLA-4 antibody 527 Location: Exhibit Halls A B George R. Brown Convention Center Date: Friday, Nov. 8, 2024 - Odd Number Posters Poster Hall Hours: 9 a.m.–7 p.m. Fc-enhanced anti-CTLA-4 antibody, botensilimab, enhances the efficacy of multiple therapeutic modalities in immunotherapy-refractory tumor models 720 Location: Exhibit Halls A B George R. Brown Convention Center Date: Saturday, Nov. 9, 2024 - Even Number Posters Poster Hall Hours: 9 a.m.–8:30 p.m. An additional presentation will cover AGEN1721, a first-in-class, Fc-enhanced bifunctional antibody targeting FAP and TGFβ. AGEN1721 is engineered to remodel the tumor microenvironment by depleting cancer-associated fibroblasts (CAFs) and neutralizing TGFβ’s immunosuppressive effects. By facilitating T-cell infiltration and activation, AGEN1721 effectively transforms cold tumors into "hot," immune-responsive environments. “AGEN1721 represents a breakthrough in addressing the challenges of immune-excluded tumors by targeting key elements that suppress immune activity within the tumor microenvironment,” said Dr. Chand. “The data we’re presenting at SITC 2024 highlight how AGEN1721’s dual-action approach can dismantle barriers to immune infiltration, offering renewed hope for more durable and effective responses against resistant cancers.” Featured AGEN1721 presentation: AGEN1721, a first-in-class Fc-enhanced bifunctional antibody targeting FAP and TGFβ, remodels the tumor microenvironment to overcome cancer-associated fibroblast-mediated immune suppression 1355 Location: Exhibit Halls A B George R. Brown Convention Center Date: Friday, Nov. 8, 2024 - Odd Number Posters Poster Hall Hours: 9 a.m.–7 p.m. About Botensilimab Botensilimab is an investigational human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses. Approximately 1,100 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316. About Agenus Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx). Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding its botensilimab and balstilimab programs, expected regulatory timelines and filings, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2023, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.