Atezolizumab

Keytruda, a Merck cancer immunotherapy that has become the world’s top-selling medication, is administered as an intravenous infusion over the course of 30 minutes. The pharmaceutical giant now has results from a pivotal clinical trial showing an experimental injectable version of Keytruda dosed in minutes was roughly comparable to the IV-administered drug. Merck now plans to discuss these results with regulators, laying the groundwork for potential submissions seeking approvals of the more patient-friendly subcutaneous version. Injectable Keytruda could improve access to the product with a version that’s less burdensome to both patients and clinicians. For Merck, an injectable formulation would help the company hold on to some market share and revenue that will be lost when biosimilar versions of the drug become available. In pursuing an injectable version of its blockbuster cancer drug, Merck is taking the same strategy as some other pharmaceutical companies that also face looming biosimilar competition. Pembrolizumab, brand name Keytruda, belongs to a class of immunotherapies called checkpoint inhibitors. The drug is an antibody designed to block PD-1, a protein on immune cells that keep those cells from recognizing and targeting tumors. Antibodies drugs are typically administered as IV infusions. Merck developed the injectable version of Keytruda with enzyme technology that enables intravenous drugs to be administered as injections. This technology, called Hybrozyme, comes from South Korea-based Alteogen. Consumer / Employer Health Executives on Digital Transformation in Healthcare Hear executives from Quantum Health, Surescripts, EY, Clinical Architecture and Personify Health share their views on digital transformation in healthcare. By MedCity News The results announced Tuesday are from an open-label Phase 3 test enrolled about 378 adults with advanced non-small cell lung cancer. Keytruda was evaluated as a first-line treatment. Patients were randomly assigned to receive injectable Keytruda in combination with chemotherapy or IV-infused Keytruda and chemotherapy. Both drug regimens were administered every six weeks. The main goal was to assess pharmacokinetics (PK) — how the drug distributed in the body. Without releasing specific figures, Merck said injectable Keytruda met the two main PK goals of the study, demonstrating exposure in the body that was no worse than the IV-infused formulation of the drug during the first dosing cycle and at the Keytruda’s trough concentration measured at the drug’s steady state. On secondary goals of efficacy and safety, Merck said the subcutaneous formulation was consistent with the IV formulation. Merck said these results, plus data from ongoing analyses, will be presented at an unspecified upcoming medical meeting and shared with regulatory authorities worldwide. “It is very encouraging to see positive Phase 3 results evaluating this fixed-dose combination of subcutaneous pembrolizumab, which was administered, on average, in approximately two to three minutes and has the potential to improve the patient experience as well as increase access for patients and healthcare providers compared to intravenous administration,” Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said in a prepared statement. Keytruda accounted for $21.6 billion in revenue through the first three quarters of 2024, a 17.6% increase compared to the same period in the prior year. It’s far and away Merck’s largest product by revenue and also the top-selling medication in the world. Keytruda drug faces patent expiration in 2028. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech Merck isn’t the only company that has turned to Alteogen’s technology as a way to try to compete against biosimilars. Earlier this month, Daiichi Sankyo secured rights to use the technology to develop a subcutaneous version of Enhertu, a blockbuster antibody drug conjugate cancer therapy that is commercialized in partnership with AstraZeneca. But Alteogen also has alliances with companies that are developing biosimilars. Sandoz has global rights to use the Alteogen technology to develop a subcutaneous version of an unspecified biosimilar in its portfolio. That deal includes an option for Sandoz to license the technology for two additional products. Roche has already received FDA approvals for new injectable formulations of two of its blockbuster products. In September, the FDA approved an injectable version of the pharma giant’s cancer immunotherapy Tecentriq. That approval was followed by a regulatory nod for an injectable formulation of multiple sclerosis drug Ocrevus. Both Roche products were developed with Enhanze, a Halozyme drug delivery technology that enables biologic drugs to be administered as injections.

Both novel bifunctional (SON-1411) and monofunctional (SON-1400) fusion proteins exhibit wild-type binding to the IL-18 receptor (IL-18Rc), coupled with undetectable binding to the inhibitory IL-18 binding protein (IL-18BP) IL-18 has significant importance for cancer immune-oncology and combination with IL-12 on Sonnet’s FHAB platform which Sonnet believes could present an important oncology possibility The lock-and-load flexibility of the FHAB platform offers the bifunctional payload capability of adding another synergistic biologics target to IL-18 generating multiple novel cancer drugs Nov. 06, 2024 -- Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) (the "Company" or "Sonnet"), a clinical-stage company developing targeted immunotherapeutic drugs, announced today that the United States Patent and Trademark Office (USPTO) has issued U.S. Patent No. 12,134,635 entitled “Interleukin 18 (IL-18) Variants and Fusion Proteins Comprising Same,” covering two of its novel drug candidates, SON-1411 (IL-18BPR-FHAB-IL12) and SON-1400 (IL-18BPR-FHAB), each containing a modified version of recombinant human interleukin-18 (IL-18BPR = Binding Protein Resistant). The patent carries a term effective until June 2044. “The issuance of this intellectual property is an important milestone that we believe provides significant differentiation from competitors trying to tap the full biological potential of IL-18, either alone or in combination with IL-12. IL-18 is a key cytokine that, when combined synergistically with IL-12, has the potential to be an important therapeutic asset for oncology and cell-based therapy,” commented Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer. SON-1411 is a proprietary bifunctional fusion protein consisting of IL-18BPR combined with single-chain wild-type IL-12, linked to Sonnet's Fully Human Albumin Binding (FHAB®) platform, which has replaced SON-1410 as a development target. SON-1400 is a monofunctional fusion protein comprising the same IL-18BPR domain linked to the FHAB. FHAB extends the half-life and biological activity of linked molecules by binding native albumin in the serum and targets the tumor microenvironment (TME) through high affinity binding to glycoprotein 60 (gp60) and the Secreted Protein Acidic and Rich in Cysteine (SPARC). IL-18 can regulate both innate and adaptive immune responses through its effects on natural killer (NK) cells, monocytes, dendritic cells, T cells, and B cells. IL-18 acts synergistically with other pro-inflammatory cytokines to promote interferon-γ (IFN-γ) production by NK cells and T cells. Systemic administration of IL-18 has been shown to have anti-tumor activity in several animal models. Moreover, tumor-infiltrating lymphocytes (TILs) express more IL-18 receptors than other T cells. However, IL-18 clinical trials have shown that, although it is well tolerated, IL-18 has poor efficacy in the treatment of cancers, most likely due in large part to the high co-expression of IL-18 binding protein (IL-18BP) in the TME. In particular, IL-18BP serves as a “decoy receptor” that binds to IL-18 with higher affinity, compared with the IL-18Rc complex, thereby causing a negative feedback loop with IL-18 and inhibiting IL-18-mediated TIL activation. Thus, there exists a potential for the discovery of IL-18 variant compositions that could harness the therapeutic potential of IL-18 for the treatment of cancers. Sonnet’s strategy for amino acid modifications to rIL-18 was based on a compilation of literature review, 3D X-ray crystallography structures, and computer modeling analysis. Subsequently, certain IL-18 variant sequences were synthesized, engineered into expression constructs and manufactured at small scale in either CHO cell culture or E. coli. Highly purified milligram quantities of SON-1411 or SON-1400 were analyzed in vitro for IL-18Rc or IL-18BP binding activities, respectively, using the HEK-Blue™ and Bright-Glo Luciferase™ IL-18Rc reporter assays. In vitro results for at least one variant of IL-18 showed equivalent binding to the IL-18 Rc, compared to the wild-type IL-18 reference molecule, concomitant with no or reduced binding to IL-18BP. The known MOA of IL-18 inhibition by IL-18BP is reviving the importance of clinical applications of IL-18. IL-18BP has been shown to be elevated in cancer patients, thus nullifying the clinical applications of IL-18. Sonnet is developing two novel bifunctional cytokine molecules, IL-18BPR-FHAB-IL12 and IL-18BPR-FHAB, both of which contain a unique IL-18 domain that does not bind the inhibitor IL-18BP but still maintains full IL-18 and IL-12 bioactivity. The clinical application of these mono or bifunctional fusion proteins could potentially expand immunotherapy applications for cancer patients. SON-1411 is a candidate immunotherapeutic recombinant drug that is closely related to and has replaced SON-1410. SON-1410 links an unmodified single-chain human IL-18 and an unmodified IL-12 with the albumin-binding domain of the single-chain antibody fragment A10m3. The key difference between SON-1410 and SON-1411 is that in the latter, there has been novel modification of the IL-18 domain via mutagenesis to retain wildtype binding to the IL-18 receptor (IL-18 Rc) while inhibiting or abolishing binding to the IL-18 binding protein (IL-18 BP). The A10m3 scFv was selected to bind both at normal pH, as well as at the acidic pH that is typically found in the TME. The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of IL-18 and IL-12, as well as a variety of potent immunomodulators that can be added using the platform. Interleukin-12 can orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as SPARC and gp60, several types of cancer such as non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant for this approach. SON-1411 is designed to deliver IL-18BPR and IL-12 to local tumor tissue, turning ‘cold’ tumors ‘hot’ by stimulating IFNγ, which activates innate and adaptive immune cell responses and increases the production of Programed Death Ligand 1 (PD-L1) on tumor cells. Sonnet is an oncology-focused biotechnology company with a proprietary platform for developing targeted biologic drugs with single or bifunctional action. Known as FHAB (Fully Human Albumin Binding), the technology utilizes a fully human single chain antibody fragment (scFv) that binds to and "hitch-hikes" on human serum albumin (HSA) for transport to target tissues. Sonnet's FHAB was designed to specifically target tumor and lymphatic tissue, with an improved therapeutic window for optimizing the safety and efficacy of immune modulating biologic drugs. FHAB platform is the foundation of a modular, plug-and-play construct for potentiating a range of large molecule therapeutic classes, including cytokines, peptides, antibodies and vaccines. Sonnet’s lead program, SON-1010, or IL-12-FHAB, is in development for the treatment of solid tumors and ovarian cancer. SON-1010 is being evaluated in an ongoing Phase 1/2a study through a Master Clinical Trial and Supply Agreement, along with ancillary Quality and Safety Agreements, with Roche in combination with atezolizumab (Tecentriq®) for the treatment of Platinum-Resistant Ovarian Cancer (PROC). The Company is also evaluating its second program, SON-1210, an IL12-FHAB-IL15 for solid tumors, in collaboration with the Sarcoma Oncology Center to commence an investigator-initiated and funded Phase 1/2a study for the treatment of Pancreatic Cancer. The Company’s SON-080 program is a low dose of rhIL-6 in development for CIPN and DPN. SON-080 demonstrated encouraging results in a Phase 1b/2a clinical trial, being well tolerated with no evidence of a pro-inflammatory cytokine response. Sonnet is currently seeking partnership opportunities to support a Phase 2 trial. The content above comes from the network. if any infringement, please contact us to modify.