Discover International’s Post

Ultimovacs provides update from Phase I study in malignant melanoma: Continued strong overall survival in patients treated with UV1 cancer vaccine and pembrolizumab ·     All patients in the trial who were alive at 3 years remain alive at 4 years (69.5%) with a minimum follow-up period of 4 years (median 53.0 months) ·      The expected next key milestone for UV1 is the readout of the FOCUS trial during Q3 2024, in which the treatment combination is the same as in the UV1-103 trial     Oslo, June 11 2024: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-stage biotechnology company developing immunotherapeutic cancer vaccines, today announced encouraging overall survival (OS) data from both cohorts in the UV1-103 Phase I clinical trial in malignant melanoma. The UV1-103 study evaluates Ultimovacs’ universal cancer vaccine, UV1, in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab, as first-line treatment in patients with advanced non-resectable or metastatic malignant melanoma. The study enrolled 30 patients in the U.S. in two cohorts that differed only in the concentration of GM-CSF used as vaccine adjuvant. With a minimum follow-up of 4 years (median 53.0 months), the updated OS results show that all patients who were alive at the 3-year mark remain alive at 4 years, with an OS rate of 69.5%   Ultimovacs has previously reported data showing a complete response rate in the UV1-103 study of 33% (complete disappearance of tumors) and an objective response rate of 57% (complete or partial disappearance of tumors). Biomarker analyses reported in October 2022 showed robust clinical responses in patients treated with the combination of UV1 and pembrolizumab, regardless of patients’ PD-L1 status. The safety profile of UV1 in combination with pembrolizumab is comparable to that of pembrolizumab alone.   “We are encouraged by the strong overall survival rate observed in this Phase I study,” said Jens Bjørheim, Chief Medical Officer at Ultimovacs. “The data show a high survival rate among patients enrolled in the UV1-103 trial, even after a minimum of 4 years of follow-up. We look forward to the read-out of the FOCUS trial in head and neck cancer, where the same treatment combination has been used”.

BioNTech SE has not clearly stated why it decided not to proceed with the Phase 3 development of acasunlimab, but liver toxicity, as mentioned by Madeleine Armstrong, might be a significant reason. BioNTech's oncology strategy seeks strong synergies within its internal portfolio, so it likely wants to avoid drugs with notable toxicities. Additionally, acasunlimab's efficacy as a monotherapy is not particularly strong, and even though one arm of the bispecific antibody targets PD-L1, it still requires pembrolizumab. Various Phase 1 clinical data for PD-L1×4-1BB drugs have been released, but there are few promising indications for this mechanism. Acasunlimab is being developed for R/R NSCLC, the only indication where it has shown multiple responses as a monotherapy. Applying the same logic, Merus N.V.'s MCLA-145 would be developed for GI cancer, and I-Mab Biopharma/ABL Bio Inc.'s ragistomig would be developed for PROC. Can the hints observed in some clinical trials provide a rational basis for setting the late-stage clinical strategy for this class of drugs? On the other hand, BNT327/PM8002 has shown promising efficacy as a monotherapy, and the combination therapy data with chemotherapeutics across various indications is also appealing. https://lnkd.in/gPf8GPhn

1. Pipeline Updates and Strategic Shifts In the collaborative project with Genmab, BNT313/GEN1053 (CD27-HexaBody) has been removed from the pipeline, while BNT315/GEN10553 (OX40-HexaBody) has been newly added. Since introducing BNT327 from Biotheus Inc., BioNTech SE has prioritized combination therapies with ADC drugs, the first being the combination with BNT325. 2. Personalized cancer vaccines typically require 6-8 weeks for manufacturing. This limitation can be a hurdle when applying cancer vaccines to metastatic cancer patients. However, combining personalized cancer vaccines with drugs that can control the disease for a certain period might be beneficial. BioNTech is particularly interested in ADC drugs as combination therapy partners for their cancer vaccines. One key question is whether ADCs capable of inducing immunogenic cell death can promote epitope spreading when combined with cancer vaccines. 3. Discontinuation of acasunlimab Research BioNTech and Genmab have discontinued their collaboration on acasunlimab. BioNTech expects more opportunities within its internal portfolio, particularly with BNT316 and BNT327, rather than with the clinical data of acasunlimab in 2L NSCLC. 4. Differentiation from Summit Therapeutics, Inc. The differentiation of BNT327 from Summit Therapeutics' ivonescimab lies in their approach. While both ivonescimab and BNT327 potentially share similar mechanisms, BioNTech pursues a technology-agnostic approach and possesses a diverse oncology toolkit. This diversity allows BioNTech to explore combination therapies that can synergize across various indications. 5. Anticipated Oncology Combination Strategies BioNTech highlights BNT327 + BNT325 and BNT211 + CARVac among the anticipated oncology combination strategies. The combination therapy of PM8002 and ADC is expected to synergize by normalizing blood vessels through PM8002, thereby enhancing the infiltration of immune cells and ADC drugs into the tumor. 6. Clinical Trial Design for BNT327 BioNTech is unlikely to restrict the clinical trial design of BNT327 to PD-L1-positive populations only. Combining chemotherapy and BNT327 has shown clinically significant efficacy in PD-L1 negative populations in specific indications, such as TNBC and SCLC.

FDA Approves #Pembrolizumab Plus Chemo for Endometrial Cancer #Merck's Pembrolizumab (#Keytruda) was the best selling pharmaceutical drug in the world in 2023, with sales of more than $25 billion. It works as a immune checkpoint inhibitor. Here’s a briefing of its mechanism of action: 1. Antigen Presentation: Antigen-presenting cells (APCs) such as dendritic cells display antigens from cancer cells. 2. T Cell Activation: T cells (specifically cytotoxic T lymphocytes, CTLs) recognize these cancer antigens as foreign or abnormal. 3. PD-1/PD-L1 Interaction: Normally, to prevent excessive immune response and maintain self-tolerance, there's a regulatory mechanism where programmed cell death protein 1 (PD-1) on T cells interacts with programmed death-ligand 1 (PD-L1) on cancer cells. This interaction inhibits T cell activation and reduces immune response against cancer cells. 4. Keytruda Intervention: Keytruda binds to PD-1 on T cells, blocking the PD-1/PD-L1 interaction. 5. Enhanced Immune Response: By blocking PD-1, Keytruda prevents the cancer cells from deactivating the T cells. This allows the activated T cells to mount a stronger immune response against the cancer cells. 6. Cancer Cell Destruction: Activated T cells can now recognize and attack cancer cells, leading to their destruction. A. Pembrolizumab (Keytruda) combined with chemotherapy is now approved for treating primary advanced or recurrent endometrial carcinoma, independent of mismatch repair (#MMR) status. B. This approval signifies the first use of immunotherapy in the initial treatment of this condition, irrespective of MMR status. C. Results from the phase 3 NRG-GY018/KEYNOTE-868 study (NCT03914612) demonstrated improved survival with Pembrolizumab plus chemotherapy compared to chemotherapy alone. The FDA has approved pembrolizumab in combination with standard chemotherapy and subsequently as a single-agent treatment for patients with primary advanced or recurrent #endometrial cancer. This approval allows for a dual approach using pembrolizumab throughout the treatment regimen for these patients.

ImmunityBio, Inc. Announces FDA Approval of ANKTIVA®, First-in-Class IL-15 Receptor Agonist for BCG-Unresponsive Non-Muscle Invasive Bladder Cancer Designated an FDA Breakthrough Therapy, the novel immunotherapy ANKTIVA activates the body’s natural killer (NK) and killer T-cell immune system to attack tumor cells Therapy stimulates memory T cells, leading to long duration of complete response exceeding 47 months and ongoing to date, with a median duration of response yet to be determined The percentage of patients with durable responses at 12 and 24 months exceeded the benchmark for magnitude of clinically meaningful results established by experts at the International Bladder Cancer Group (IBCG) ANKTIVA in combination with BCG is approved for maintenance therapy for up to 37 months with tolerable side effects ranging from 0% to 3% Grade 3/4 adverse events ANKTIVA is expected to be available in the U.S. by mid-May 2024  Conference call and webcast are expected to be held April 26 at 11:00 am EDT CULVER CITY, Calif., April 22, 2024 — ImmunityBio, Inc. (NASDAQ: IBRX), an immunotherapy company, today announced that the U.S. Food and Drug Administration (FDA) has approved ANKTIVA (N-803, or nogapendekin alfa inbakicept-pmln) plus Bacillus Calmette-Guérin (BCG) for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors. “The FDA’s approval of ANKTIVA marks our launch of a next-generation immunotherapy beyond checkpoint inhibitors,” said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. “ANKTIVA not only proliferates and activates the patient’s own NK cells and CD8+ killer T cells, but also activates CD4+ T helper cells, thus enhancing the proliferation of memory killer T cells. This novel mechanism of action, which mimics the biology of the dendtritic cell, begins the evolution of immunotherapy beyond T cells alone. The combination of the proliferation of key cancer-killing immune cells, together with the activation of T cells with memory, results in durable complete responses. The ‘triangle offense’ of tumor cell killing by the body’s immune system with long-term memory is the foundation of our efforts to develop a therapeutic cancer vaccine across multiple tumor types, regardless of the site of origin.” https://lnkd.in/ehfFBr78

Cambridge Big Biotech AstraZeneca saw its share price rise 320p to 10,414p after Tagrisso (osimertinib) – with the addition of chemotherapy – was approved in the US for the treatment of adult patients with the most common form of lung cancer. https://lnkd.in/ebzFRqhi The FDA backing covers the treatment of locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). It was based on the results from the FLAURA2 Phase III trial published in The New England Journal of Medicine. Tagrisso with the addition of chemotherapy was found to reduce the risk of disease progression or death by 38 per cent compared to Tagrisso monotherapy, which is the 1st-line global standard of care. David Fredrickson, Executive Vice-President, Oncology Business Unit, AstraZeneca, said: “This important new treatment option can delay disease progression by nearly nine additional months, establishing a new benchmark with the longest reported progression-free survival benefit in the 1st-line advanced setting. “This approval reinforces Tagrisso as the backbone of EGFR-mutated lung cancer treatment either as monotherapy or in combination with chemotherapy. “The news is especially important for those with a poorer prognosis, including patients whose cancer has spread to the brain and those with L858R mutations.” Laurie Fenton Ambrose, President and CEO, GO2 for Lung Cancer, added: “We are so excited to see this continued progress advancing more personalised treatment options for our community. The more we can target the right treatments for the right people at the right time, the better outcomes will be for our community - a goal we all collectively share.” AstraZeneca has also completed the acquisition of Icosavax, Inc., a US-based clinical-stage biopharma company focused on developing differentiated, high-potential vaccines using an innovative, protein virus-like particle platform. The deal is expected to stack up to $1.1 billion. Icosavax has become a subsidiary of AstraZeneca with operations in Seattle. The acquisition will build on AstraZeneca's expertise in respiratory syncytial virus (RSV), strengthening its Vaccines & Immune Therapies late-stage pipeline with Icosavax's lead investigational vaccine candidate, IVX-A12. 

Diakonos Oncology CFO Anthony Baldor is at #BIO24 this week to make a company presentation and meet with potential partners and investors. For those interested in learning more about Diakonos’ unique dendritic cell vaccines for cancer, we can be reached through the BIO ONE Partnering System. Mr. Baldor’s company presentation takes place on Tuesday, June 4th at 3:00 pm PT in Company Presentation Theater 2 at the San Diego Convention Center. Mr. Baldor’s presentation will include a review of Diakonos’ highly differentiated double-loaded autologous dendritic cell vaccines for cancer, and an operational update on the company’s plans for growth, including clinical development outlook and expansion of its leadership team. Diakonos recently completed a Phase 1 trial of DOC1021, its lead vaccine for glioblastoma multiforme (GBM), and is planning a Phase 2 study. The US Food and Drug Administration has granted Fast Track and Orphan Drug status for DOC1021. Two other clinical trials are under way with dendritic cell vaccines targeting pancreatic cancer and angiosarcoma. “We are very excited about the results of our Phase 1 trial for GBM,” Mr. Baldor said. “Data observed to date give us great confidence in our dendritic cell vaccines and their potential to treat a broad range of solid tumor cancers, including the most deadly. Twelve month survival is currently at 90% for evaluable patients, and the therapy is well tolerated.” Diakonos’ dendritic cell vaccines activate robust cytotoxic TH1 cell signaling pathways that better harness a patient's immune system to target and eliminate cancer cells by initiating a natural immune response. This is achieved without any genetic modification of the patient’s immune cells, which greatly simplifies the manufacturing process and significantly reduces costs when compared to leading cell therapy approaches. Visit our we site: diakonosoncology.com to learn more. #cancerresearch #cancer #biopharma #clinicaltrials https://lnkd.in/dET5pqbD

Could Cancer Vaccines Be the Next Big Breakthrough in Immunotherapy? Oncology remains the major focus area in R&D for large pharma companies as global spending in the area continues to grow. Immunotherapies, in particular, have quickly become some of the best-selling products on the market. Seeking ever more efficacious treatments, companies are now eyeing cancer vaccines, which experts say could be more powerful than other immunotherapies and may even provide a preventative measure against certain malignancies. The first therapeutic cancer vaccine was approved in 2010, and Dendreon’s Provenge is still the only therapy of this type on the market. But interest in the space is growing as certain candidates enter late-stage clinical trials. “It’s definitely a competitive area,” said Scot Ebbinghaus, vice president of clinical research at Merck, which is developing mRNA-4157/V940 in partnership with Moderna. “But competition is a good thing for patients. It makes us work harder and smarter. We look carefully at what our competitors are doing. https://lnkd.in/e-aKJUPG

Bispecific antibodies (BsAbs) have been among the most promising novel modalities in recent years. Of the 11 BsAbs approved in Oncology to date, 9 were approved between 2021–2023 — clear evidence of the significant momentum in the industry pipeline. Last year a string of FDA approvals of T-cell engagers (TCEs), arguably the most prominent type of BsAbs currently, brought new treatment options for patients with heavily pretreated heme malignancies. 📍DLBCL: Epkinly (epcoritamab; CD20xCD3), Columvi (glofitamab; CD20xCD3) 📍Multiple myeloma: Talvey (talquetamab; GPRC5DxCD3), Tecvayli (teclistamab; BCMAxCD3), Elrexfio (erlanatamab; BCMAxCD3) Recent clinical data for PSMA-directed TCEs in prostate cancer as well as DLL3-directed TCEs in small cell lung cancer show the enticing potential of this modality in solid tumors as well, a considerably larger opportunity. 𝗪𝗵𝗮𝘁 𝗺𝗮𝗸𝗲𝘀 𝗕𝘀𝗔𝗯𝘀 𝘀𝗽𝗲𝗰𝗶𝗮𝗹? BsAbs are capable of mediating therapeutic effects beyond those of monospecific antibodies by recruiting immune effector cells to cancer cells, for example, or by targeting different signaling pathways with a single molecule. Importantly, BsAbs can exert multiple MOAs simultaneously and offer a valuable alternative antibody platform in immunotherapy treatment. 𝗕𝘀𝗔𝗯𝘀 𝗮𝗽𝗽𝗿𝗼𝘃𝗲𝗱 𝗼𝗿 𝗶𝗻 𝘁𝗵𝗲 𝗰𝗹𝗶𝗻𝗶𝗰: BsAb-mediated dual modulators of signaling pathways, tumor-targeted receptor agonists, BsAb–drug conjugates, bispecific T cell, natural killer (NK) cell and innate immune cell engagers, bispecific checkpoint inhibitors and co-stimulators 𝗡𝗲𝘅𝘁-𝗴𝗲𝗻𝗲𝗿𝗮𝘁𝗶𝗼𝗻 𝗕𝘀𝗔𝗯𝘀 𝗶𝗻 𝗲𝗮𝗿𝗹𝗶𝗲𝗿 𝗱𝗲𝘃𝗲𝗹𝗼𝗽𝗺𝗲𝗻𝘁: Trispecifics, BsAb prodrugs, BsAbs that induce degradation of tumor targets, BsAbs acting as cytokine mimetics #oncology #innovation

NEW ARTICLE: Johnson & Johnson to acquire $2 billion drug developer "Ambrx Biopharma" to treat Turbo Cancers with same tech as Pfizer's $43 billion Seagen acquisition. Both set their sights on 2025 Cancer TSUNAMI Pfizer & Moderna COVID-19 mRNA Vaccines cause Turbo Cancers, this is now well acknowledged by respected physicians around the world. Last month, Pfizer closed a $43 billion acquisition of Seagen, to boost its ability to treat 7 of the top 10 Turbo Cancers caused by its COVID-19 mRNA Vaccine. Top 5 Turbo Cancers: lymphoma, glioblastoma, breast, colon, lung Top 10 Turbo Cancers: leukemia, melanoma, sarcomas, testicular/ovarian, kidney Pfizer expects a "Cancer Tsunami" to hit in 2025 Moderna is rushing its melanoma mRNA Cancer vaccine to have expedited approval by 2025. Johnson & Johnson is the latest to want a piece of the Turbo Cancer treatment pie before 2025. This $2 billion acquisition of Ambrx Biopharma gives them the same cancer treatment tech as Pfizer - ADCs. ADC: "a class of therapeutics that combines the specificity of monoclonal antibodies with the potency of cytotoxic drugs, aiming to target and destroy cancer cells more effectively" Johnson & Johnson, for $2 billion, adds new ability to treat Breast Turbo Cancer, Prostate Turbo Cancer and Kidney Turbo Cancer with this acquisition. Iulian urban pe mewe