On April 7, 2024 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported three-year follow-up data from a Phase 1 trial with the mRNA-based individualized neoantigen-specific immunotherapy ("iNeST") candidate autogene cevumeran (also known as BNT122, RO7198457) in patients with resected pancreatic ductal adenocarcinoma ("PDAC") (Press release, BioNTech, APR 7, 2024, View Source [SID1234641837]). The data show that in 8 out of 16 patients autogene cevumeran elicited an immune response up to three years post administration measured by activated T cells. The persistence of T cels was associated with a longer median recurrence-free survival in cancer vaccine responders.

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"These new data are an early signal for the potential of our individualized mRNA cancer vaccine approach in this indication with an unmet medical need. The results indicate that our uridine mRNA-LPX technology can promote activation of cytotoxic T cells that may help to eliminate residual tumor foci at early stages of the disease to delay or prevent recurrence," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "Our ongoing Phase 2 trial with Genentech aims to confirm these findings on benefit for patients with PDAC compared with the current standard of care treatment in the post-surgical, adjuvant setting in a larger patient population. We remain committed to our vision of personalized cancer medicine and aim to help advance the standard of care for many patients."

The results featured in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting 2024 show the following:

In 8 of 16 patients, autogene cevumeran elicited high-magnitude T cells specific to the encoded neoantigens.
98% of the T cells targeting individual neoantigens on the tumor and induced by autogene cevumeran were de novo in that they were not detected in blood, tumors, and adjacent tissues prior to administration of the investigational treatment.
Over 80% of the vaccine-induced neoantigen-specific T cells could still be detected up to three years post administration in patients with an immune response. These patients showed a prolonged median recurrence-free survival compared to non-responders.
6 of 8 patients with an immune response to autogene cevumeran remained disease free during the three-year follow-up period, while 7 of the 8 patients without an immune response to the treatment during the trial showed tumor recurrence.
The investigator-initiated, single center Phase 1 trial (NCT04161755) evaluated the safety of autogene cevumeran in sequential combination with the anti-PD-L1 immune checkpoint inhibitor atezolizumab and standard-of-care chemotherapy in 16 patients with resected PDAC. Data from the 1.5-year median follow-up were published in Nature in May 2023. The current data update includes a three-year median follow-up and was presented in a late-breaking oral presentation at the AACR (Free AACR Whitepaper) Annual Meeting 2024 in San Diego, California, by principal investigator Vinod Balachandran, M.D., surgeon-scientist at Memorial Sloan Kettering Cancer Center and principal investigator of the study.

An ongoing open-label, multicenter, randomized Phase 2 trial (NCT05968326), sponsored by Genentech in collaboration with BioNTech, was started in October 2023. The trial will investigate the efficacy and safety of adjuvant autogene cevumeran in combination with the anti-PD-L1 immune checkpoint inhibitor atezolizumab and chemotherapy compared with the current standard of care chemotherapy (mFOLFIRINOX) in patients with PDAC. The Phase 2 trial is currently enrolling patients at clinical trial sites in the United States, with additional sites planned to open globally. Autogene cevumeran is being jointly developed by BioNTech and Genentech and is currently being evaluated in three ongoing randomized Phase 2 clinical trials in adjuvant PDAC (as mentioned above), first-line melanoma, and adjuvant colorectal cancer.

About resected pancreatic ductal adenocarcinoma (PDAC)
PDAC is amongst the leading causes of cancer-related deaths in the United States4 with approximately 90% of patients dying within two years of their diagnosis5. A combination of surgical removal and systemic cytotoxic chemotherapy has shown to improve clinical outcomes; however, even with surgical resection, the relapse rate remains high, and the 5-year overall survival is only approximately 20%6 in patients who undergo surgery followed by adjuvant chemotherapy ("ACT") and only 8-10%i,ii in those who do not receive ACT. Thus, there is an unmet medical need for novel therapies for patients with resected PDAC.

About iNeST (individualized Neoantigen Specificimmuno Therapy)
iNeST immunotherapies are investigational individualized cancer therapies tailored to a specific patient’s tumor. They contain unmodified, pharmacologically optimized mRNA encoding up to 20 patient-specific neoantigens, identified using real-time next-generation sequencing and bioinformatic neoantigen discovery. Neoantigens are proteins that are produced by cancer cells that differ from the proteins produced by healthy cells and are recognized by immune cells. The mRNA is encapsulated in BioNTech’s proprietary intravenous RNA-lipoplex delivery formulation which is designed to enhance stability as well as enable targeted delivery to dendritic cells. By analyzing each patient’s tumor, BioNTech is able to identify the cancer mutations that may act as neoantigens. Each individual cancer vaccine encodes for neoantigen candidates with the highest likelihood of helping the immune system recognize the cancer. For this purpose, BioNTech has developed an on-demand manufacturing process, following Good Manufacturing Practice (GMP) conditions. Autogene cevumeran is currently being evaluated in various solid tumor indications, including three Phase 2 clinical trials in first-line melanoma, adjuvant colorectal cancer, and adjuvant pancreatic ductal adenocarcinoma.

An iNeST Fact Sheet and images from the iNeST manufacturing process are available in the newsroom section on BioNTech’s website at this link.

On April 5, 2024 Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of light and/or radiation activated Photo Dynamic Compounds ("PDCs") for the safe and effective destruction of various cancers, bacteria and viruses, reported that it has been granted a Canadian patent for a new cancer vaccine (Press release, Theralase, APR 5, 2024, View Source [SID1234644093]).

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The recently issued patent is titled, "Vaccine Containing Cancer Cells Inactivated by Photodynamic Treatment with Metal-Based Coordination Complexes and Immunotherapy Method Using Same".

A US patent protecting the same technology was previously issued in October 2022. A European Union patent is currently pending.

The patent protects Theralase PDC technology in the treatment of a patient with a cancer vaccine; specifically, programmed to destroy their cancer.

This is fundamentally accomplished by obtaining a sample of their cancer and treating it extracorporeally with a Theralase PDC and then activating the PDC with either light or radiation. This inactivated cancer is then injected back into the patient intravenously, programming the patient’s immune system to recognize, attack and destroy the particular cancer of interest.

Theralase’s pipeline includes: a Phase II registration clinical study for bladder cancer expected to be completed in 2026, plans to launch a Phase Ib clinical study for both brain cancer and lung cancer in 2024, pending completion of a toxicology analysis, and now after the issuance of a Canadian and US patent on a cancer vaccine, the ability to treat various "liquid cancers"; such as leukemia, lymphoma and myeloma.

Dr. Arkady Mandel, MD, PhD, DSc, Chief Scientific Officer of Theralase, inventor of the patent stated, "The issuance of an additional patent for our cancer vaccine technology represents a significant opportunity for patients diagnosed with blood-related cancers, which are difficult, if not impossible, to treat. Our primary focus has been on the research and development of technology to destroy solid-core tumours, such as bladder, brain and lung cancers; however, this new patent allows the Company the opportunity to explore the treatment of various liquid cancers."

Roger DuMoulin-White, President and Chief Executive Officer of Theralase stated, "The possibilities and opportunities of our PDC technology continue to grow at a rapid pace. The Company plans to become properly financed this year through various equity and debt instruments to allow the Company the opportunity to commence new clinical studies focused on the destruction of both solid-core and liquid cancers. I am excited about the opportunities available to the Company, as a result of these new patents, as it significantly increases the opportunity for our PDC technology to treat patients inflicted with a wide range of cancers."

About Leukemia:
Leukemia is a cancer that starts in the stem cells of blood. As the stem cells of the blood develop, they become blast cells (blasts), which are immature blood cells. In leukemia, there is an overproduction of blast cells. These blast cells develop abnormally and don’t develop into mature blood cells. Over time, the blast cells crowd out normal blood cells so that they can’t do their jobs.

Leukemia is the 11th most common cancer in the United States. As of 2019, more than 470,000 Americans have a history of leukemia. It was estimated that about 60,000 people would be diagnosed with leukemia in 2022. The five-year relative survival rate of leukemia is 65.7%.

About Lymphoma:
Lymphoma is a type of cancer that occurs due to the malignant transformation of the lymphocytes (infection fighting cells of the immune system). The most common category of lymphoma, Non-Hodgkin Lymphoma ("NHL") is the 7th most common cancer in the United States. In 2024, the American Cancer Society’s estimates 80,620 people (44,590 males and 36,030 females) will be diagnosed with NHL. The five-year relative survival rate of lymphoma is 72%.

About Myeloma:
Myeloma, also known as multiple myeloma, is a type of blood cancer that develops from plasma cells in the bone marrow. Myeloma is the 14th most common type of cancer. In 2023, an estimated 35,730 adults in the United States will be diagnosed with multiple myeloma. The overall 5-year survival rate for people with multiple myeloma in the United States is 55%.

About RuvidarTM:
RuvidarTM is a peer-reviewed, patented PDC currently under investigation in a Phase II registration clinical study for bladder cancer.

On April 5, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported an analysis from the IMvigor011 study that was presented at the European Association of Urology (EAU) Congress 2024 in Paris, France (Press release, Natera, APR 5, 2024, View Source [SID1234641836]). The analysis evaluates outcomes in muscle-invasive bladder cancer (MIBC) patients who tested serially negative with Signatera, Natera’s personalized and tumor-informed molecular residual disease (MRD) test.

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Sponsored by Genentech, a member of the Roche group, IMvigor011 is a global, double-blind, randomized, Phase III trial, in which high-risk MIBC patients are serially tested with Signatera for up to 12 months post cystectomy. Patients who test Signatera MRD-positive at any point during the 12-month surveillance window are randomized to the anti-PDL1 atezolizumab (Tecentriq) vs. placebo. Patients who remain Signatera-negative at completion of the testing window are not randomized but continue to undergo radiographic imaging thereafter.

The analysis presented at the EAU Congress evaluated clinical outcomes in 171 high-risk MIBC patients who entered screening for IMvigor011 and remained MRD-negative during the surveillance window. Key takeaways from the presentation include:

Overall survival (OS) rates of 100% at 12 months and 98% at 18 months, in patients who remained serially MRD-negative.
Disease-free survival (DFS) rates of 92% at 12 months and 88% at 18 months, in patients who remained serially MRD-negative.
Concludes that patients who remain MRD-negative on serial testing may be spared from adjuvant treatment.
"IMvigor011 is an important randomized study that is designed to address a critical unmet need for the more than 35,000 patients a year diagnosed with muscle-invasive bladder cancer," said John Simmons, vice president, BioPharma at Natera. "We believe the results of this trial will further demonstrate how Signatera can help personalize treatment decisions and improve outcomes for bladder cancer patients. Together with Professor Powles and our collaborators at Genentech, we look forward to the full trial read-out which could serve as the basis of Natera’s first FDA companion diagnostic submission for Signatera."

This presentation follows a study published in Nature based on the phase III randomized IMvigor010 trial, which showed that patients who tested Signatera MRD-positive after radical cystectomy received significant benefit from adjuvant immunotherapy with atezolizumab, while Signatera-negative patients derived no significant benefit from adjuvant therapy.

As previously announced in October 2023, Natera submitted the first module of its premarket approval application to the U.S. Food and Drug Administration (FDA) for Signatera as a companion diagnostic (CDx) assay for patients with MIBC.

Note: Tecentriq (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group.

About Signatera
Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer and muscle-invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 50 peer-reviewed papers.

On April 5, 2024 BPGbio, Inc., a leading biology-first AI-powered biopharma that focuses on oncology, neurology, and rare diseases, reported the application of its NAi Interrogative Biology Platform across several drug and diagnostic applications, following successful collaborations with Stanford University, University of Tennessee, Oak Ridge National Laboratory, and several leading hospitals across Mexico (Press release, BPGbio, APR 5, 2024, View Source [SID1234641835]). The company will present four posters showcasing these research collaborations and provide updates on other internal research activities at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 5-10, 2024, in San Diego, Calif.

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Highlights from posters include:

New data further validating the mitochondrial-centric effect of BPM31510 on the immune system. In addition to its direct cell-killing effect on tumor cells, data supports the potential use of BPM31510 in the intersection of tumor immunology and tumor metabolism
BPGbio’s NAi Platform coupled with a subsequent deep learning algorithm implemented on BRG399, a novel pan-cancer drug candidate, can improve efficiency in drug development by rapidly predicting anti-cancer efficacy in silico before conducting resource intensive preclinical experiments
A new study in Mexico further validating the utility of BPGbio’s prostate cancer biomarker, the pstateDx test, which was discovered by the NAi Platform, in an independent population
New data validating UBE2M, a novel potential therapeutic target for cancer, identified by the NAi Platform.
"Our company has pioneered and proliferated a unique biology-first approach to the use of AI in drug discovery and development as we focus on high unmet disease indications," said Niven R. Narain, Ph.D., President and CEO, BPGbio, Inc. "Our NAi Interrogative Biology platform has guided our development team via many successful research collaborations enabling us to deliver positive clinical trial readouts across multiple indications in various stages of development. Our goal is to offer potential and hope to patients and families facing ravaging diseases like GBM and pancreatic cancer."

Presentation Details:

Abstract 3527: Application of deep learning-based drug sensitivity prediction model on a novel anticancer drug
Presentation: Monday, April 8, 2024, 1:30-5:00 p.m. in Poster Section 35

Abstract 3751: Diagnostic assessment of Filamin A (FLNA) as a serum biomarker for identification of benign prostatic hyperplasia vs. aggressive prostate cancer in a prospective Mexican cohort
Presentation: Monday, April 8, 2024, 1:30 – 5:00 p.m. in Poster Section 44

Abstract 4694: In charge: Targeting neddylation of UBE2M for anticancer therapy
Presentation: Tuesday, April 9, 2024, 9:00 a.m. – 12:30 p.m. in Poster Section 28

Abstract 6518: BPM31510: Targeting the tumor microenvironment (TME) via mitochondrial-mediated ROS production
Presentation: Tuesday, April 9, 2024, 1:30 – 5:00 p.m. in Poster Section 47

About the NAi Interrogative Biology Platform

The NAi Interrogative Biology Platform combines BPGbio’s industry-leading, clinically annotated proprietary biobank, purpose-built Bayesian artificial intelligence, and the compute power of the world’s fastest supercomputer, Frontier, housed at Oak Ridge National Laboratory. Collectively, these tools enable the company to bring artificial intelligence to biology inspiring AI-driven target nomination, discovery, molecule design, and more. The platform has been used to identify more than 100 drug targets and diagnostic biomarkers and supported research collaborations with a range of government, industry and academic partners including the U.S. Department of Defense, Sanofi, and Harvard Medical School.

About BPM31510

BPM31510 is BPGbio’s lead candidate in late-stage development for glioblastoma multiforme (GBM) and pancreatic cancer. The compound has demonstrated a tolerable safety profile and shown potential clinical benefit in both populations. The mechanism of action of BPM31510 was first validated by data from BPGbio’s NAi Interrogative Biology platform, which suggested that there is a hallmark shift in the tumor microenvironment (TME) induced by BPM31510 which modulates mitochondrial oxidative phosphorylation in highly aggressive tumors.

About BRG399

BRG399, a BPGbio-developed oral experimental drug with favorable pharmacological properties for clinical testing, is a first in class anti-mitotic agent with broad-spectrum anti-cancer activity. BRG399 is being studied for its therapeutic potential as a treatment for solid and liquid tumor cancers as well as diseases associated with inflammation. BPGbio’s scientists reported that the anti-mitotic activity of BRG399 is the result of an inhibition of microtubule polymerization.

About pstateDx

​​BPGbio’s pstateDx test is the first diagnostic product discovered by the company’s AI-powered NAi Interrogative Biology platform to be commercially launched. The pstateDx test is a non-PSA based, unique molecular diagnostic blood test that measures filamin A, a key biological driver of prostate cancer. The test provides a risk score to help clinicians differentiate between BPH and aggressive prostate cancer at the time of initial screening. It may help reduce unnecessary biopsies in the BPH population, where men are sometimes repeatedly biopsied even though they do not have prostate cancer.

On April 5, 2024 Nucleai, a spatial AI biomarker company that deciphers cellular conversations and maps cellular interactions within tissue samples to predict therapeutic outcomes, reported it will showcase its developments in cancer research and diagnostics at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego, California from April 5-10, 2024 (Press release, Nucleai, APR 5, 2024, View Source [SID1234641834]). Nucleai’s posters will highlight novel AI spatial biomarkers and enhanced histopathology workflows that promise to revolutionize cancer treatment and diagnostics.

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Nucleai’s first poster, in collaboration with Arutha Kulasinghe, PhD, senior research fellow, Frazer Institute, University of Queensland, Australia, where he also leads the Clinical-oMx Lab, unveils the identification of a novel signature linked to immunotherapy treatment outcomes in lung cancer. Leveraging Nucleai’s unique AI spatial biology solution, the research uncovered the correlation between the metabolic state and spatial distribution of tumor and immune cells in the tumor microenvironment, shedding new light on treatment outcomes and potential resistance mechanisms. This discovery holds the promise of improving immunotherapy response rates by providing crucial insights into disease progression, treatment response, resistance mechanisms, and the development of more effective therapeutics and diagnostics. Nucleai is driving innovation in cancer research and collaborating with leading scientists to translate these findings into tangible benefits for patients and healthcare providers worldwide.

Poster #1158 on Sunday, April 7 from 1:30 to 5:00 PM
Nucleai’s second poster introduces the H&E 2.0 algorithm, a significant advancement in cancer pathology. This advanced algorithm, trained on spatial biology technologies such as multiplex immunofluorescence, sets a new standard for precision and depth in disease management and treatment selection. Unlike traditional AI solutions, H&E 2.0 augments manual pathologist annotations, enabling the automated identification of rare and hard-to-detect cell types in patient tissue biopsies. By implementing the H&E 2.0 algorithm, pathologists can automate challenging tasks, improve accuracy and scalability, and extract deeper insights from existing biobanks of H&E-stained clinical samples. This solution marks a leap toward more precise and efficient cancer diagnosis and treatment selection.

Poster #3518 on Monday, April 8 from 1:30 to 5:00 PM
Oscar Puig, PhD, Vice President, Translational Medicine & Diagnostics of Nucleai, said of the significance of the AACR (Free AACR Whitepaper) posters: "Our collaborations and innovation are pushing the boundaries of spatial biology; they are redefining the standards in cancer research and diagnostics. The breakthroughs we’re unveiling at AACR (Free AACR Whitepaper) epitomize the potency of merging innovative machine learning algorithms with pioneering spatial biology techniques to ensure cancer care is more resolute than ever so we can improve patient outcomes and have a positive impact on the lives of patients with cancer."

Dr. Kulasinghe said, "Our study has unveiled a unique metabolic signature in tumor cells that is closely linked to immunotherapy resistance and overall survival in lung cancer patients. This discovery, rooted in the century-old Warburg effect, sheds light on how the functional and metabolic activity of tumor cells causes them to proliferate aggressively and develop resistance to immunotherapy. By identifying patients with this tissue signature, we could personalize treatment strategies, for example, giving them combination therapies, to improve outcomes. This research represents a significant leap forward in our understanding of cancer metabolism and its implications for personalized medicine."

Nucleai’s advanced spatial biology and AI-driven platform enhance pathology by extracting deeper insights from pathology slides. This approach enhances the precision of medicine, accelerates drug development, and improves patient care. By integrating spatial biology with AI, Nucleai creates actionable insights from complex pathology data, setting a new standard for diagnosis and treatment, and advancing precision medicine.

For more information about Nucleai’s presence at AACR (Free AACR Whitepaper), you can visit nucleai.ai/aacr2024