Altasciences Co., Inc.

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. '

Biotechnology accelerates drug discovery and offers innovative approaches to dealing with some of humanitys most important healthcare challenges. In fact, recent reports indicate that over 50% of drug development comes from biotech innovation. By their nature, biotechs are inventive and often rely on various solution providers to complete the drug development process and bring their therapeutic discoveries to patients. CRO SupportContract research organizations (CROs) offer a unique value proposition for biotech companies; biotech firms can leverage their role as innovation leaders to form strategic partnerships with CROs, which can provide essential support for their research and development needs. That said, the success of any working partnership depends on choosing the right partner. According to a 2022 McKinsey & Company report, biotech companies are looking to partner with CROs that can deliver strategic advice and leading-edge drug development solutions. A CRO with extensive expertise across various therapeutic areas and solutionsfrom preclinical to formulation and manufacturing to clinical researchand that provides lean and agile service delivery, would effectively meet many of the needs of biotech firms.Additionally, leading CROs have established relationships with key drug development players, which can benefit biotechs. Strong connections with global regulatory authorities and understanding of regulatory guidelines, for example, allow open communication and pertinent strategic guidance. CROs typically also have robust networks of patients, caregivers, and other clinical trial resources that will support a biotech companys development goals, from discovery through clinical trials. Long-Term VisionBiotech companies often outsource therapeutic development to different providers who deal with each need (from preclinical, to clinical to bioanalysis to manufacturing) as it arises. The downside with this approach is a lack of continuous, long-term vision, multiple meetings and constant cross communication as well as the administrative burden of negotiating and managing contracts with multiple service providers. By contrast, early engagement with a top-tier, multi-service CRO/CDMO like Altasciences, working under a single nondisclosure agreement (NDA) across services and a single master service agreement (MSA), provides efficiency, cross-functional insight, seamless communication, and scheduling and continuity that easily transfers across the development continuum. The Value of PartnershipPartnering with a single, dedicated CRO/CDMO that offers preclinical, clinical, bioanalytical, and CDMO expertise provides biotech companies with access to coordinated early data and information, ensuring informed and timely downstream decision-making. A CRO partner offering multiple drug development solutions gains better visibility into the program's progress, allowing the program manager to share insights, strategies, and solutions with the client as the project evolves.Steve Mason, Co-chief Operating Officer of Altasciences, says, Its really about timely communication and having the systems and processes to manage all ongoing studies and programs to safely get to the deliverable faster, without compromising on quality.By building a long-term partnership with a CRO that offers the services they need, biotech companies can shift from a focus on transactional contracts in the short term to optimizing costs and building value in the long term. As early development demands faster timelines, earlier proof of concept, and cost efficiencies, biotechs rely on the greater breadth and depth of capability that multi-service, integrated CRO/CDMOs offer to maximize their probability of success.Models for Successful PartnershipIntegrated CROs are increasingly prioritizing partnerships, customizing solutions, and redefining their processes to maximize value for their clients. There is a wide range of contracting models available, such as one-off projects, preferred provider, and strategic partnership agreements, strategic staffing, and full-service models. The more agile CROs offer tailored blended models to suit their clients needs based on size, budget, capacity, and development stage. When a sponsor works with a CRO with a specific area of focus or expertise, theyre working with a CRO that is mostly invested in what happens to that therapeutic in that moment and rarely considers the next phases of development, explains Steve Mason, Co-chief Operating Officer at Altasciences. That presents a challenge for sponsors as theyll have to collaborate with many, many CROs before meeting their end goal.Whether a biotech company's long-term goal is marketing approval or divestment, the success of its drug development programs relies on efficient and agile early development, supported by effective partnerships. An integrated, multi-service early development CRO, having successfully managed hundreds or even thousands of programs, brings invaluable combined knowledge and experience to facilitate the biotech's work. A partnership model that provides guidance, leadership, and access to expertise when needed, steering the biotech towards its intended goal, is a significant contribution a CRO offers. '