Algorithme Pharma, Inc.

Welcome to Endpoints News’ manufacturing briefs, where we bring you essential news on new builds, collaborations, recalls and more. National Resilience is replacing its CEO effective immediately with COO William Marth, who will take over from Rahul Singhvi. Marth previously served as CEO of Curia Global, known then as AMRI, as well as CEO of Teva Pharmaceutical’s US division. Moderna has opened its new mRNA manufacturing facility in Australia within the campus of Monash University. The new site will be able to make 100 million vaccine doses a year, and the first dose is anticipated to be produced next year. Around 140 new “direct” jobs will be created at the site. Reckitt Benckiser is pouring £155 million ($200 million) into a new facility in Wilson, NC, to make its over-the-counter flu and cold drug products, the company said Tuesday. This will be Reckitt’s largest OTC manufacturing site in the US and will create 300 new jobs. CDMO Cambrex is partnering with Eli Lilly’s biotech innovative arm, dubbed Lilly Catalyze360-ExploR&D, to offer its services to Lilly’s biotech partners, according to a Thursday release. Agenus has revealed its planning to make layoffs as a part of its wider plan to reduce costs, the company said Thursday. The company said Monday it is restructuring its manufacturing sites to become a biologics CDMO. Nature’s Toolbox has secured $15 million from JP Morgan to fund the development of its manufacturing platforms to make biomaterials, the company said Wednesday. Altasciences is the manufacturer for several of Metsera’s weight loss candidates, the company said on Nov. 28. The CDMO has produced the biotech’s Phase 1/2 GLP-1 asset, dubbed MET-097i. It is also making two other candidates for Metsera: a long-acting amylin analog (MET-233i) and an oral GLP-1 drug (MET-002). Rallybio is moving its C5 inhibitor into a confirmatory study next year following manufacturing improvements, the company said Monday. After data analysis and changes to the production of the drug, named RLYB116, the study will be completed in the second quarter of 2025. GE Healthcare is gaining full ownership of the radiopharma manufacturer Nihon Medi-Physics by buying Sumitomo Chemical’s 50% stake in the company, according to a Sunday release. The transaction is expected to close early next year. Telix IsoTherapeutics has renewed its supply agreement with clinical-stage radiopharma Plus Therapeutics, according to a Tuesday release. Telix will continue to supply rhenium-186 isotopes for Plus’ lead candidate, obisbemeda, which is being studied for CNS tumours. Eckert & Ziegler is supplying the radiopharma company Ariceum Therapeutics with actinium-225 and lutetium-177 for its lead asset, satoreotide, under study for hard-to-treat cancers. KBI Biopharma will manufacture Alanis Therapeutics’ preclinical antibody that is being investigated for myelodysplastic syndromes and acute myeloid leukemia, according to a Tuesday release. CELLforCURE by SEQENS is partnering with clinical-stage biotech Smart Immune, according to a Tuesday release. The CDMO will make the biotech’s Phase 1/2 asset, SMART101, for acute leukemia or primary immunodeficiencies. NorthX Biologics will make Amarna Therapeutics’ clinical-stage gene therapy called Nimvec AM510, which is being investigated for type 1 diabetes, according to a Tuesday announcement. API manufacturer Antheia will receive $12 million from the US Department of Health and Human Services over two years to manufacture an unnamed pharma ingredient domestically, according to a Tuesday release. Lonza’s ADC company Synaffix has entered a licensing agreement with DNA sequencer Illumina, the companies said Wednesday. Synaffix’s so-called “metal-free clock chemistry” tech will be used by Illumina for its DNA sequencing products. Chemical manufacturer LG Chem is collaborating with microbiology biotech Acies Bio on sustainable commercial production of chemicals in high demand, the companies said Thursday. The UK Health Security Agency has signed a contract with CSL Seqirus to manufacture five million doses of human H5 influenza vaccines for the UK, the agency said Tuesday. The Brazilian research organization Oswaldo Cruz Foundation signed a memorandum of understanding with Belgian companies Quantoom Biosciences and Univercells to boost production of RNA therapeutics in Belgium, according to a Friday release. Gavi, the Vaccine Alliance, is investing $23.4 million to help vaccinate children in Sudan, in partnership with Save the Children and UNICEF, according to a Monday release. The funding will in part be used to improve vaccine storage and cold supply chains. With additional reporting by Katherine Lewin

Cancer research is experiencing a paradigm shift with the introduction of innovative therapies like messenger RNA (mRNA)-based treatments and chimeric antigen receptor T-cell (CAR T) therapy. The development and use of immunotherapy and precision medicine have sparked global interest due to their potential to harness the body's immune system to fight cancer more effectively. Both therapies have demonstrated promising outcomes in clinical trials, particularly in refractory cancers. Advances in targeted cancer therapies are integral to improving overall remission rates and reducing damage to healthy tissues, explains Dr. Beatrice Setnik, PhD, Chief Scientific Officer at Altasciences.Crucial nonclinical data gathered from mRNA and CAR T-studiesNonclinical studies in mRNA and CAR T-cell therapy are essential for evaluating the efficacy and safety of these cutting-edge therapies before they reach first-in-human clinical trials. Assessing endpoints such as potential toxicities, dose-limiting effects, immune responses, on-tumor and off-target activities, biodistribution and persistence, and the presence and severity of cytokine release syndrome (CRS) ensures that the therapies target cancer cells effectively without harming healthy tissues. With a comprehensive understanding of the therapeutic mechanisms and risks, sponsors can prioritize resources for their most viable compound, as well as determine safe dosages and therapeutic windows for their clinical trial design, explains Dr. Norbert Makori, Vice President of Toxicology at Altasciences. Clinical research on CAR T-cell therapy: Changing the dynamic of cancer treatmentIn CAR T-cell therapy, a patients T cells are engineered to express a synthetic receptor (the CAR) that targets specific antigens on cancer cells. The FDA has approved this type of immunotherapy for certain hematologic cancers, and ongoing clinical trials are exploring its application in other malignancies.Several CAR T-cell therapies, such as tisagenlecleucel and axicabtagene ciloleucel, have been FDA-approved for B-cell malignancies like acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma. Clinical trials in these cancers have reported long-term remission in patients who had been non-responsive to other treatments. Current developments include:Ongoing Clinical Trials in Solid Tumors: Solid tumors often present a hostile microenvironment that suppresses immune responses and can cause CAR T-cells to malfunction or become exhausted. They also present physical barriers that make it difficult for CAR T-cells to reach the tumor site. Nevertheless, clinical trials are underway to evaluate the use of CAR T-cells for treating solid tumor cancers, where researchers are focused on identifying suitable targets for CAR T-cell therapy, such as HER2 in breast cancer and EGFR in lung cancer.Next-Generation CAR T-Cells: Clinical research is advancing towards creating next-generation CAR T-cells with enhanced functionality. One field of inquiry is the development of CAR T-cells that target more than one antigen (dual-targeting CARs) or have switch receptors that act against repressing signals from the tumor microenvironment. Another area is the design of allogeneic (off-the-shelf) CAR T-cells, which would allow for the treatment of multiple patients with a single product, without the need for individualized cell engineering.Toxicity and Safety Concerns: Clinical trials have identified two major safety concernsCRS and neurotoxicity. CRS results from an exaggerated immune response, where cytokines are released in large quantities. Severe cases can cause inflammation, rash, low blood pressure, high fever and organ damage. Neurotoxicity can lead to confusion, seizures, or coma in severe cases. Researchers are exploring methods of mitigating these side effects, such as administering drugs like tocilizumab (an IL-6 receptor blocker) or steroids during treatment.Clinical development of mRNA-based cancer therapiesmRNA-based cancer therapies involve delivering synthetic mRNA into cells to instruct them to produce proteins that trigger an immune response. Clinical research in this area is focused on developing mRNA cancer vaccines and immune modulators that enhance the body's natural tumor-defense capabilities.mRNA Cancer Vaccines: Early clinical trials have mainly focused on testing mRNA vaccines against various cancers, including melanoma, lung cancer and colorectal cancer. For example, BioNTech initiated clinical trials with its mRNA-based cancer vaccine BNT111 for advanced melanoma. These trials have demonstrated that mRNA vaccines can stimulate robust immune responses by activating cytotoxic T cells specific to tumor-associated antigens.Moderna is investigating mRNA-4157, a personalized cancer vaccine, which is being administered in combination with immune checkpoint inhibitors such as pembrolizumab, for the treatment of solid tumors. Preliminary results from Phase I trials showed favorable safety profiles and signs of antitumor activity in certain patient groups.Combination Therapies: Research into how mRNA vaccines work in combination with other therapies, like checkpoint inhibitors or CAR T-cell therapy, is in the early phases of clinical testing. The rationale is that mRNA vaccines can induce a strong initial immune response, while checkpoint inhibitors or CAR T-cells can enhance and sustain the attack on the tumor. Challenges in Clinical Trials: Delivery of mRNA into cells, particularly in solid tumors, is a significant hurdle; lipid nanoparticle (LNP) delivery systems are being optimized to improve the stability of mRNA and ensure targeted delivery to the desired cells. Managing the immune response to avoid excessive inflammation or autoimmune reactions is another area where researchers are testing chemical modifications to mRNA molecules to reduce these side effects.Future directions As understanding of personalized and targeted medicine grows, we can except personalized cancer vaccines, sometimes used in combination with other therapies. CAR T-cell therapy will likely expand to target solid tumors, improving precision and reducing side effects in cancer treatment. This research is at the forefront of medical discovery, carrying with it the hope of delivering lasting benefits for people worldwide. '

Glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) are entero-pancreatic hormone-based treatments first approved in 2005 for type 2 diabetes (T2D). They are now commonly prescribed for weight loss and reduction of atherosclerotic cardiovascular (CV) risk in patients with T2D.The health benefits and market success of GLP-1 drugs are a hot topic in todays pharmaceutical landscape. According to a MarketWatch reportfrom February 2024, the global GLP-1 market is expected to reach $471 billion by 2032.As of February 2024, there were 15 GLP-1 medications approved by the FDA for glycemic and weight control, and more were already in development.More than one billion peopleworldwide are living with obesity, which puts them at risk of major health complications, such as T2D, high blood pressure, heart disease, stroke, metabolic syndrome, fatty liver diseases, some cancers, kidney disease, breathing problems, and sleep apnea. Most of these diseases are interrelated, with glycemic control and weight loss being a major factor in improving the overall health of sufferers.We are in an era where combinations of entero-pancreatic hormones can deliver significant weight loss, and patients are experiencing health benefits well beyond blood sugar management and weight loss.As we learn more about GLP-1 RAs, we realize that they target many organ systems, including the pancreas, the stomach, brain, heart, kidneys, immune system (due to reduced inflammation), skeletal muscle, control of metabolism of both white and brown adipose tissue, and positive effect in fatty liver disease (nonalcoholic fatty liver disease and steatohepatitis; MAFLD and MASH), says Dr. Gaetano Morelli, Chief Medical Officer at Altasciences.What GLP-1 is and how receptor agonists workDr. Gaetano Morelli explains, GLP-1 is a hormone called an incretin or gut peptide released by endocrine cells in the small intestine in response to nutrient ingestion, mainly glucose and fat.Clinical data on GLP-1 RAsGLP-1 RAs mimic the action of endogenous GLP-1 and, in head-to-head clinical studies, have demonstrated that all GLP-1 RAs are effective at reducing A1C levels. These initial pivotal studies that led to the first wave of GLP-1 RAs demonstrated that they work in several ways, including stimulating insulin release, slowing digestion, reducing appetite, and inhibiting glucagon release.A guidancefrom the U.S. FDA (draft updated in March 2020) requires data on cardiovascular events in new T2D drug development programs. As a result, dedicated cardiovascular safety trials were implemented. Many demonstrated beneficial effects of GLP-1 RAs on the heart and kidneys in patients with T2D (with and without preexisting conditions), with those effects thought to be largely independent of glucose-lowering.More recently, pharmaceutical companies have sponsored large cardiovascular outcomes trials (CVOTs) to assess the beneficial effects of GLP-1 RAs on the cardiovascular system in patients with T2D, with encouraging results.What comes nextLooking to the next generation of clinical trials for obesity treatments, we see combinations of GLP-1 RAs with other entero-pancreatic hormones with complementary actions and/or synergistic potential (such as glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin) to enhance the weight loss and cardiometabolic benefits of GLP-1 RAs. There are currently more than 140 of such compounds in development. Drug developers are also investigating the potential for longer-lasting injections.Oral formulations are another future enhancement for GLP-1 RA medicines, with several pill forms in development. Various physiological barriers, such as mucus, intestinal, and enzymatic barriers, interfere with the oral delivery or absorption of protein and peptide-based therapeutics. Thus, novel approaches such as nanocarriers, site-specific, and stimuli-specific delivery, are being used to improve the success of oral GLP-1 RAs.Sources indicate that newer GLP-1s have fewer side effects, although the most common gastrointestinal issues (nausea, vomiting, and diarrhea) may continue. Loss of muscle mass, often associated with rapid weight loss, is another potential side effect being investigated. Long-term side effects of GLP-1 usage are currently unknown, and researchers are accumulating data as this therapeutic area continues to boom.Promising programs have been halted due to challenges with side effect profiles and drug interactions, and diligent, expert program development will be critical as we move into the next generations of these important therapeutics, says Dr. Morelli. Developing newer and better GLP-1 RAs is a crucial contribution to global human health, and it is a field we at Altasciencesare proud to be advancing. '