PDL1

CEL-4000 may deliver safe and effective therapy for RA by rebalancing the inflammatory response, without weakening important immune defense mechanisms, risking infections or cancer, as current treatments may VIENNA, Va.--(BUSINESS WIRE)-- CEL-SCI Corporation (NYSE American: CVM) today announced the peer reviewed scientific journal Frontiers in Immunology published an article regarding CEL-SCI’s Ligand Epitope Antigen Presentation System (LEAPS) technology in the treatment of rheumatoid arthritis (RA) titled: “Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccines”. CEL-SCI’s LEAPS team, along with outside collaborators from U.S. and Europe, reviewed published/presented results from pre-clinical animal model of antigen-specific LEAPS therapeutic vaccines, such as CEL-4000 and CEL-5000, made specific for the treatment of RA, and compared these findings with published results of other RA-therapies that either suppress or alter the immune response in order to treat RA. In the article, the authors note that the currently available therapeutic arsenal for the treatment of RA consists mainly of immunosuppressive or ablative drugs, which may carry the potential risk of facilitating recurrent or primary infectious diseases or cancer. They also underscore that a therapeutic vaccine that can rebalance the inflammatory disease process, promoting antigen-specific disease-directed T cell immune responses, is highly desirable. CEL-4000, an antigen specific immunomodulating vaccine, is provided as a new treatment paradigm that should deliver therapy for RA without weakening important immune defense mechanisms against microbial infections or cancer. The authors also emphasized that the most appropriate way to advance the LEAPS vaccines to the clinic would be an adaptive study design for clinical trials, enrollment of patients with early-stage RA, and using the Bayesian optimal design model, currently used in oncology studies, as well as the use of disease-related biomarkers to ascertain responsiveness to treatment and introduce additional tools to assess outcome at the disease level. “At CEL-SCI, we focus on utilizing a healthy immune system to overcome disease safely and with minimal side effects. Our LEAPS platform, and CEL-4000 specifically approaches the treatment of auto immune diseases like rheumatoid arthritis in a completely different way. By rebalancing the immune system to its original healthy state, CEL-4000 could protect patients from the risk of cancer and infection,” stated CEL-SCI CEO, Geert Kersten. “The growing body of preclinical data on LEAPS supports the advancement of this asset into human studies.” About CEL-SCI Corporation CEL-SCI believes that boosting a patient’s immune system while it is still intact should provide the greatest possible impact on survival. Multikine* (Leukocyte Interleukin, Injection) is designed to help the immune system "target" the tumor at a time when the immune system is still relatively intact and thereby thought to be better able to mount an attack on the tumor. In a Phase 3 study, CEL-SCI studied patients who were newly diagnosed with locally advanced primary squamous cell carcinoma of the head and neck (oral cavity and soft-palate) with the investigational product Multikine administered first, before they received the standard of care, which involved surgery followed by either radiation or chemoradiation. The Phase 3 study enrolled 928 patients. Our approach is unique because most other cancer immunotherapies are administered only after conventional therapies have been tried and/or failed. After analyzing data from the Phase 3 study, we have better defined the target head and neck cancer population for Multikine, which is advanced primary head and neck cancer patients with no lymph node involvement and with low PD-L1 tumor expression. In the Phase 3 study, we observed statistically significant survival data in the final target population, showing that Multikine cut the risk of death in half at five years vs control. We plan to submit the proposed study protocol to the FDA in Q1 2024, with the goal to get FDA buy-in for a confirmatory clinical trial, and also to discuss potential accelerated approval pathways. Multikine (Leukocyte Interleukin, Injection) received Orphan Drug designation from the FDA for neoadjuvant therapy in patients with squamous cell carcinoma (cancer) of the head and neck. The Company has operations in Vienna, Virginia, and near/in Baltimore, Maryland. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. When used in this press release, the words "intends," "believes," "anticipated," "plans" and "expects," and similar expressions, are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Such statements include, but are not limited to, statements about the terms, expected proceeds, use of proceeds and closing of the offering. Factors that could cause or contribute to such differences include an inability to duplicate the clinical results demonstrated in clinical studies, timely development of any potential products that can be shown to be safe and effective, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital and the risk factors set forth from time to time in CEL-SCI's filings with the Securities and Exchange Commission, including but not limited to its report on Form 10-K for the year ended September 30, 2023. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. * Multikine (Leukocyte Interleukin, Injection) is the trademark that CEL-SCI has registered for this investigational therapy. This proprietary name is subject to FDA review in connection with the Company's future anticipated regulatory submission for approval. Multikine has not been licensed or approved for sale, barter or exchange by the FDA or any other regulatory agency. Similarly, its safety or efficacy has not been established for any use.

AstraZeneca and GSK aim to bring their PD-1/L1 combinations to a broad front-line endometrial cancer population. After a quick FDA approval in a subset of endometrial cancer, GSK is back with more data for two Jemperli regimens in hopes of reaching a broader patient population. And AstraZeneca, utilizing a similar immunotherapy strategy, has also come up with a rivaling update as it awaits an FDA decision. For GSK, Jemperli plus chemotherapy showed a “clinically meaningful trend” in reducing the risk of death by 21% among patients with advanced endometrial cancer that’s mismatch repair proficient (pMMR) or microsatellite stable (MSS). Patients on the Jemperli regimen lived a median 34 months, compared with 27 months for those on chemo alone. The data, from an exploratory analysis of the first part of the phase 3 RUBY trial, were shared at the Society of Gynecologic Oncology (SGO) annual meeting. They come as part of a statistically significant overall survival win for the Jemperli-chemo combo in the overall trial group as it cut the risk of death by 31% in a broader endometrial cancer population that also includes patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) tumors. With the updated analysis from RUBY Part 1, GSK said it expects the FDA will accept its submission to expand the PD-1 inhibitor Jemperli to the overall front-line endometrial cancer population in the first half of this year. The Jemperli-chemo combo was already greenlighted in July just for dMMR/MSI-H patients, who account for about 15% to 20% of new advanced endometrial cancer diagnoses in the U.S. Simultaneously, Part 2 of the RUBY trial found that a cocktail of Jemperli, chemo and GSK’s PARP inhibitor Zejula reduced the risk of progression or death by 37% in pMMR/MSS patients, according to data shared at SGO 2024. For the overall population, which also includes dMMR/MSI-H patients, the risk reduction was 40%. The Part 2 findings are particularly meaningful for patients with pMMR/MSS tumors as they further improved on the benefit observed for the Jemperli-chemo regimen in Part 1, Mansoor Raza Mirza, M.D., from the Copenhagen University Hospital and RUBY principal investigator, said in a statement Saturday. Previously, Jemperli and chemo cut the risk of progression or death by 24% versus chemo in the pMMR subgroup. However, the Part 2 data also raised the question of whether the further addition of Zejula is necessary for dMMR/MSI-H patients. Among that subset of patients, the Zejula-Jemperli-chemo combo showed a 52% advantage in progression-free survival over chemo alone, which was even smaller than the impressive 72% risk reduction Jemperli-chemo had posted without the PARP drug. Zejula appears to have brought extra toxicity. In Part 1, grade 3 or higher treatment-emergent adverse events were about 12% higher for Jemperli and chemo compared with control. In Part 2, the Zejula-containing regimen tripled that difference to about 36%. The potential longer-term detriment from PARP inhibitors have lately drawn attention at the FDA, leading to market withdrawal, restricted new approval or delayed application.  A GSK spokesperson said the company was unable to provide additional details about its regulatory plans at this time. Meanwhile, AstraZeneca could face the same question of patient selection for its PD-L1 inhibitor Imfinzi and Merck-shared PARP drug Lynparza in first-line endometrial cancer. In an interim analysis of AZ’s phase 3 DUO-E trial shared at SGO 2024, a combination of Imfinzi, Lynparza and chemo cut the risk of death in dMMR/MSI-H endometrial cancer patients by 72% over chemo, a slight improvement from the 66% posted by the Imfinzi-chemo pairing. None of these numbers were mature or statistically significant. Previously, the trial found that the Lynparza-containing regimen reduced the risk of progression or death by 59% over chemo alone, whereas Imfinzi and chemo could already cut that risk by 58%, according to results announced in October. In the overall trial population that also includes pMMR patients, the Imfinzi-chemo pairing so far cut the risk of death by 23%, whereas the Lynparza-containing regimen delivered a 41% showing. Again, the data were immature as only 28% of deaths had happened across the three trial arms before a final overall survival analysis. The overall survival data are promising at this early stage of maturity, Andrea Mugan, AstraZeneca’s global franchise head of gynecological and genitourinary cancers, said in an interview with Fierce Pharma. As PARP inhibitor’s contribution in dMMR tumors comes into question, AZ also faces the question of whether Imfinzi could handle pMMR disease without Lynparza. During the current interim analysis, Imfinzi plus chemo only pared down the risk of death by 9% in pMMR patients, while adding Lynparza widened that to 31%. Imfinzi-chemo showed a progression-free survival benefit of 23% in this subgroup, versus 43% for the Lynparza regimen, according to data first released in October. “We do believe in the data we’re showing for the benefit of both regimens in the first-line endometrial cancer population,” Mugan said. But she acknowledged that Imfinzi showed the biggest benefit in the dMMR population, and that the “incremental benefit” for Lynparza was more pronounced in the pMMR subgroup. AZ’s filings for DUO-E have been accepted by the FDA, the European Medicines Agency and regulators in Japan, the company said. It’s not clear whether AZ is gunning for approvals for both regimens for both dMMR and pMMR cancers.

-- Tunlametinib is poised to be a potential best-in-class MEK inhibitor based on positive data from the pivotal Phase 2 study SHANGHAI, March 18, 2024 /PRNewswire/ -- KeChow Pharma, a commercial-stage pharmaceutical company focused on developing and commercializing differentiated small molecule therapeutics for cancer, today announced that the China National Medical Products Administration (NMPA) has approved tunlametinib (HL-085) for the treatment of patients with NRAS mutated advanced melanoma who were previously treated with PD-1/PD-L1. This is the first approved targeted therapy for this patient population and the first product originated from KeChow's in-house research and development activities since the company's inception. The new drug application (NDA) of tunlametinib was previously granted priority review by the Center for Drug Evaluation (CDE) of the NMPA. The approval was based on the results of a multicenter, single-arm, phase II, pivotal registrational study which conducted in 100 patients in China (NCT 05217303). Clinical efficacy data of tunlametinib in China, as assessed by independent radiological review committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, include an overall response rate (ORR) of 35.8%, median progression free survival (PFS) of 4.2 months, and disease control rate (DCR) of 72.6%. Subgroup analysis showed that in patients who had previously received immunotherapy, the ORR was 40.6%. The most common treatment-related skin event was rash (53%), followed by dermatitis acneiform (24%). The most common grade ≥3 TRAE in this study was blood creatine phosphokinase increased (38.0%), which was mostly asymptomatic and manageable with dose modification [1]. "We are excited and proud of this major milestone for KeChow. Tunlametinib, approved in China, is the first internally designed and developed molecule by KeChow team ." said Dr. Hongqi Tian, Founder, Chief Executive Officer and Chairman of KeChow. "The approval of tunlametinib is an important milestone to provide new treatment option for Chinese patients with NRAS-mutated advanced melanoma who previously received PD-1/PD-L1. We would like to express our sincere gratitude to the clinicians and patients who participated in our trials, and we thank the health authorities for their strong support. We are committed to making tunlametinib available in China as soon as possible to serve this patient population." "We own the worldwide rights to tunlametinib. KeChow has a comprehensive clinical development plan to evaluate tunlametinib as a monotherapy and in combination with other standard of care therapies to treat multiple cancers including melanoma, neurofibromatosis type 1–related plexiform neurofibromas, colorectal cancer, and non-small cell lung cancer in China," said Dr. Hongqi Tian. "We look forward to expanding the product potential of tunlametinib through establishing partnerships on a worldwide basis." Melanoma is one of the most common cutaneous cancers. There are an estimated 20,000 newly diagnosed melanoma patients in China each year [2]. NRAS mutations accounted for 10.4~12.6% of melanoma patients in China [3], and 15-25% globally [4-7]. NRAS-mutated melanoma is more aggressive and associated with poorer outcomes [8-11]. There were no approved targeted therapies for patients with NRAS-mutant melanoma. Tunlametinib is the first small molecule drug approved for this indication. About tunlametinib Tunlametinib is a small molecule inhibitor of Mitogen-activated protein kinase kinase (MEK) discovered and developed by KeChow. Tunlametinib targets the Mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinases (ERK) signaling pathway (also known as RAS/RAF/MEK/ERK signaling pathway) by inhibiting the activity of MEK kinase, blocking downstream signaling pathways, inhibiting the growth and proliferation of tumor cell. MAPK/ERK signaling pathway plays a critical role in cancer cell proliferation and apoptosis. Aberrant activation of this signaling pathway has been implicated in more than one-third of all malignancies. Compared to other approved MEK inhibitors, tunlametinib demonstrated stronger target inhibition and improved pharmacokinetic properties. About KeChow Pharma Shanghai KeChow Pharma, Inc. is a commercial-stage pharmaceutical company focusing on differentiated small molecule therapeutics for cancer. The company was founded by Dr. Hongqi Tian in 2014, and is headquartered in Shanghai Zhangjiang Pharmaceutical Valley. Since its inception, KeChow is committed to accelerate the discovery, development and commercialization of novel small molecule therapeutics through scientific innovation and by leveraging extensive pharmaceutical expertise from the management team. The company has a science driven corporate culture and is specialized in the development of best-in-class innovative therapeutics to address unmet medical needs of patients around the world. References SOURCE Shanghai KeChow Pharma, Inc