Bristol Myers Squibb Co.

On the hunt for new first-in-class therapeutics, Evotec and Pfizer linked up on Wednesday to conduct early R&D activities geared towards metabolic and infectious diseases. The team-up could give the German drugmaker a much needed boost as it works to return to profitability under the leadership of a new CEO.Under the multi-year master research collaboration and option and licence agreement, the partners will work together at Evotec’s Campus Curie site in France, which houses technologies for high throughput screenings, in vitro and in vivo biology assays, as well as proteomics and metabolomics. The collaboration’s goal is to “unlock new approaches to treating pervasive metabolic and infectious diseases that impact millions of patients worldwide,” said Luca Mollo, vice president and medical lead of Pfizer’s France division.Evotec will receive research support funding from Pfizer and be eligible for milestones and royalties.Strategic resetThe tie-up comes after Evotec shared an outlook for 2024 that was well below consensus estimates, disappointing investors. During its first quarter earnings report, the company also announced a strategic reset to focus on small molecules and biologics, prompting an exit from gene therapy in May. The firm is also adjusting to new leadership. Christian Wojczewski took the helm as CEO at the start of the month, following the resignation of long-term chief executive Werner Lanthaler amid allegations of undisclosed stock trades.Wednesday’s deal is Evotec’s latest partnership inked with a large drugmaker. The company also has agreements with Bayer for precision cardiovascular disease treatments; with Bristol Myers Squibb for neuroscience candidates; and with Sandoz to supply biosimilars, among others.

Pictured: 3D illustration of a T cell attacking a cancer cell/iStock, Meletios Verras Interius BioTherapeutics announced Tuesday that it has secured a regulatory go-ahead to conduct a first-in-human Phase I trial for its potentially first-in-class in vivo CAR-T therapy for B cell malignancies. The Philadelphia-based biotech will conduct its trial in Australia after the Human Research Ethics Committee for the country’s Therapeutic Goods Administration granted the company its Clinical Trial Notification clearance. Interius expects to initiate the Phase I study in the fourth quarter of 2024, with the expected delivery of key milestones “as early as the first quarter of 2025,” according to Tuesday’s announcement. STAT News reported that Interius is looking to enroll up to 30 patients from various sites globally. The early-stage trial is primarily designed to evaluate the safety of a single infusion of the investigational in vivo cell therapy, dubbed INT2104. The study will not be blinded and will include a dose-escalation part to determine the optimal dose of INT2104 for future trials. The decision to start trials outside the U.S. was informed by the FDA’s overly cautious approach to the in vivo therapy, Interius CEO Phil Johnson told STAT. The regulator wanted a study that could be stopped when a grade 3 safety event occurred. An FDA spokesperson in a statement to STAT said that it would be “unusual” for grade 3 events to cause an automatic pause in a study. Regardless of where the study is conducted, Johnson in a statement said that the regulatory clearance for a Phase I trial for INT2014 is a “significant milestone” for Interius and “recognizes the potential of our novel in vivo targeted gene therapy candidate.” Currently available CAR-T treatments—such as Johnson & Johnson and Legend’s Carvykti (ciltacabtagene autoleucel) and Bristol Myers Squibb’s Breyanzi (lisocabtagene maraleucel)—are ex vivo therapies. Doctors collect patients’ T cells and engineer them outside of the body, typically in specialized laboratories, to produce the CAR proteins on their surface. The modified cells are reintroduced into the patients, where the CAR proteins seek out and target antigens on cancer cells causing their destruction. Interius’ approach hopes to replicate this process—but entirely inside the patient’s body. INT2104 targets CD7-positive T and natural killer cells to deliver a CAR transgene, allowing these effector cells to bind to the CD20 antigen which is commonly found on malignant B cells. INT2104 distinguishes itself from current CAR-T therapies by providing an off-the-shelf, single-dose intravenous treatment and by eliminating the need for lymphodepletion, according to the biotech. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

LAG-3 (Lymphocyte Activation Gene-3) has emerged as a significant target in cancer immunotherapy, representing a new frontier in the ongoing efforts to harness the immune system to combat cancer. First discovered in 1990, LAG-3 is a cell surface molecule that plays a crucial role in regulating T cell function and has been identified as an important immune checkpoint. Following this, the approval to worldwide first LAG-3 inhibitor therapy; Opdualag™ (nivolumab and relatlimab-rmbw), developed by Bristol Myers Squibb, in March 2022, for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma, further aid to expand the realm as well as competitve landscape. According to Neeraj Chawla, Research Head at Kuick Research, the global market opportunity for LAG 3 drugs will surpass US$ 3 Billion by 2029 and more LAG 3 drugs are expected to enter the market by end of this decade. From clinical perspective, LAG-3 has garnered significant attention as a potential target for cancer immunotherapy. It has been found to synergize with other immune checkpoints, such as PD-1 and CTLA-4, to enhance immune evasion by tumors. This understanding has led to the development of LAG-3 inhibitors, including monoclonal antibodies that block LAG-3 and restore T cell function. Several of these inhibitors are currently undergoing clinical trials, both as monotherapies and in combination with other immune checkpoint inhibitors, showing promising preliminary results in terms of safety and efficacy across various cancer types, including melanoma, non-small cell lung cancer, and renal cell carcinoma. As well as, commercially, the LAG-3 inhibitor market is poised for growth due to augmenting triumph of approved therapy whose sales have increased twice and has crossed half a Billion-dollar sales in 2023; representing opportunism to come in pharma sector. Additionally, the potential for combination therapies that include LAG-3 inhibitors offers significant commercial opportunities, as these combinations may provide superior clinical outcomes compared to monotherapies. For that reason, many clinical trials are ongoing in the domain in order to understand the role of LAG-3 in cancer. For instance, ABL Bio, a Biotech company based in South Korea, has begun a first-in-human (FIH) phase 1 open-label, multicenter, multiple-dose, dose-escalation and dose-expansion study of ABL501 to evaluate the safety, tolerability, MTD and/or RP2D, PK, immunogenicity, preliminary anti-tumor activity, and the PD effect of ABL501 in subjects with any progressive locally advanced (unresectable) or metastatic solid tumors. It is an interventional study (NCT05101109) which has an estimated enrollment of 36 participants, begun in October 2021 and will be completed by December 2024. Accompanied with clinical trials, many preclinical contenders targeting LAG-3 have been developed. Like, Y Biologics has developed a novel, cutting-edge mono- specific LAG-3 therapy, YBL-011 which is currently in the preclinical stage for the treatment of solid tumors. Above this, the global interest in LAG-3 therapies is influencing immunotherapy market, as multinational pharmaceutical companies seek to collaborate with local firms and tap into the advanced research capabilities available in the global segment. This international collaboration not only enhances the technological exchange but also opens up the new investment and growth opportunities. Such as, in June 2024, Immutep, an Australian based company, announced that it has settled into a clinical trial collaboration as well as supply agreement with Merck through a subsidiary with the foremost obejctive to access eftilagimod alfa (efti) in combination with anti-PD-1 therapy, Keytruda (pembrolizumab) along with chemotherapy for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) in a pivotal Phase III trial. In nutshell, targeting LAG-3 in cancer therapy represents a promising avenue for enhancing anti-tumor immune responses and overcoming resistance to current immunotherapies. The ongoing clinical trials in addition to robust commercial interest underscore the potential impact of LAG-3 inhibitors in the evolving landscape of cancer treatment, although continued research and clinical validation are essential to fully realize their therapeutic potential.