Member Info for 5085

Interesting read on PSA

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764268/

A long read but there are some amazing snippets in here

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216232/

I don't think there is a 'forced seller' Stephen just has a massive amount of shares. It will all rebalance in time.

Episwitch has already produced exciting results in REFINE ALS

https://alsnewstoday.com/news/episwitch-test-may-help-classify-als-patients-new-trial-data/

Only a few weeks away

https://www.pmwcintl.com/session/clinical-dx-showcase_2024sv/

Https://remissionmedical.com/prismra-and-vectra-diagnostic-blood-tests/

"Unfortunately, until now, there has been no way to tell who is a false positive. PSE has a positive predictive value of 94%, so approximately 1 in 20 will be false positive — a massive improvement from 3 of 4," Burrows said. "The PSE test combines the PSA score with five epigenetic biomarkers (chemical markers on your DNA) to predict the presence or absence of prostate cancer. For each individual, the EpiSwitch technology captures personal epigenetic biomarkers that represent a systemic fingerprint of specific regulatory network changes associated with prostate cancer."

https://healthnews.com/news/device-limit-prostate-cancer-overdiagnosis/

On December 22, New York Governor Kathy Hochul signed Senate Bill 1196a / Assembly Bill 1673a into law, securing a major win for patients across New York. The new law will require all state-regulated health plans, including Medicaid, to cover comprehensive biomarker testing, which will enable more New Yorkers to access precision medicine treatments that can lead to fewer side effects, improved survival, better quality of life and potentially lower costs for patients facing cancer and other serious illnesses.

The American Cancer Society Cancer Action Network (ACS CAN) “is proud to see New York, a longstanding leader in health equity and medical innovation, join 13 other states that have recently enacted similar legislation,” said Lisa Lacasse, president of ACS CAN. “This action ensures that New York will continue to pave the way in the fight against cancer and improve access to the most effective treatments, giving patients a better chance of living longer, healthier lives.”

Biomarker testing has become a game-changing part of cancer care given its role in opening the door to personalized care, including targeted treatments that can lead to improved survivorship and quality of life.

Legislation S.1196-A/A.1673-A requires state-regulated insurance plans, including Medicaid, to cover biomarker testing for diagnosis, treatment, appropriate management, or ongoing monitoring of a patient’s disease or condition when the test is supported by medical and scientific evidence.

State Senator Roxanne Persaud said, "Biomarker testing has rapidly become an integral part of healthcare, as research has shown that it drastically improves outcomes for patients suffering from various illnesses and conditions, including different forms of cancer, arthritis, Parkinson's, and more. After months of dedicated effort, I'm delighted that we can give millions more New Yorkers the gift of access to this life-saving treatment just as we approach the holidays. I want to thank my cosponsor, Assembly Member Pamela Hunter, Governor Kathy Hochul, the American Cancer Society, and many other organizations who enthusiastically supported this legislation and ultimately made it possible. We would not be celebrating this achievement today without the unwavering support of those organizations and individuals who recognized that this is an issue about saving lives. Access to timely diagnosis and targeted treatment has been given a huge boost, and I am proud of our accomplishment."

Assemblymember Pamela Hunter said, "As medical capabilities progress and patients begin to see greatly improved health outcomes, we should strive to make the benefits of these new advancements as equitable as possible. With biomarker tests, patients will have access to new information that will guide treatment in a way that is more tailored to the individual. Additionally, this will help conserve medical resources as patients are given treatments that are most likely to yield results instead of going through a period of trial and error. I am proud to have sponsored this bill in New York State and I thank Governor Hochul for signing this vital legislation into law to significantly broaden the availability of these lifesaving tests."

Https://www.nysenate.gov/legislation/bills/2023/A1673/amendment/A#:~:text=2023%2DA1673%20%2D%20Summary-,Requires%20health%20insurance%20policies%20and%20medicaid%20to%20cover%20biomarker%20testing,by%20medical%20and%20scientific%20evidence.

Currently, further collections and monitoring of IO responses by RECIST 1.1 and by the identified EpiSwitch predictive biomarkers have been expanded to over five hospital sites and clinical practices, from Malaysia to the US. Real life data on predictive stratifications for IO patients will further evaluate the established classification model. A pan-therapy application of the test with response prediction across tumour types with historically low ORRs could help to improve both patient outcomes and increase the cost effectiveness of cancer care [76,77].

Go to:

5. Conclusions

With the rapid advancement of novel therapies targeting the immune checkpoint pathway, there is a pressing need to develop better biomarkers to assess likely clinical response in advance of therapeutic intervention. Here, we report on a novel 3D genomics approach to identify predictive blood-based markers that can identify, with high accuracy, individuals that are likely to respond to PD-(L)1 ICIs monotherapy, especially across tumour types with low ORRs. The 3D genomics approach described here has been developed into a clinical assay to assist in treatment decisions, help improve patient selection for optimised treatment, help better utilise alternative effective treatments, minimise or avoid unnecessarily toxicity, and efficiently manage costs and resources.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216232/

EpiSwitch®is a biomarker platform and methodology for patient stratification developed on the basis of the original chromosome conformation capture (3C) approach as a novel biomarker modality [35,36]. The EpiSwitch®platform has reduced to practice all stages of the discovery, development, validation, and monitoring of blood-based biomarkers, based on 3D genome architecture. To date, 3D genomic EpiSwitch® biomarkers, also known as chromosome conformation signatures; have been used in blood test format to stratify

Melanoma patients

Prognostically stratify patients with fast versus slow progressing motor neurone disease

Stratify patients with symptomatic and pre-symptomatic neurodegenerative disease

Diagnose patients with thyroid cancer

Various stages of prostate cancer - significantly increase PSA positive predictive value in the context of prostate cancer treatment in the population at risk

Prognostically stratify patients for outcome in diffuse large B cell lymphoma

Predictively stratify patients with NSCLC for response to the anti-PD-L1 ICI Avelumab

Https://www.researchgate.net/publication/370699992_Development_and_Validation_of_Blood-Based_Predictive_Biomarkers_for_Response_to_PD-1PD-L1_Checkpoint_Inhibitors_Evidence_of_a_Universal_Systemic_Core_of_3D_Immunogenetic_Profiling_across_Multiple_Onco

The whole document is full of amazing information and data, this is just the conclusion

With the rapid advancement of novel therapies targeting the immune checkpointpathway, there is a pressing need to develop better biomarkers to assess likely clinical

Cancers 2023,15, 2696 23 of 27response in advance of therapeutic intervention. Here, we report on a novel 3D genomicsapproach to identify predictive blood-based markers that can identify, with high accuracy,individuals that are likely to respond to PD-(L)1 ICIs monotherapy, especially across tumourtypes with low ORRs. The 3D genomics approach described here has been developedinto a clinical assay to assist in treatment decisions, help improve patient selection foroptimised treatment, help better utilise alternative effective treatments, minimise or avoidunnecessarily toxicity, and efficiently manage costs and resources.

Https://www.hopkinsmedicine.org/health/conditions-and-diseases/prostate-cancer/prostate-cancer-advancements-in-screenings

The company have enough cash to see them through to the end of q1 2024

Bizarre in the extreme that no one has officially discussed the whereabouts of the missing/loaned out £20m?

Surely someone from the locked in clan has an answer.

Background

The relationship between blood biomarkers, tumor immunity, and benefit from immune checkpoint inhibitors (ICIs) is not well understood. The JAVELIN Bladder 100 trial (NCT02603432) demonstrated that avelumab 1L maintenance prolongs overall survival (OS) in pts with aUC that has not progressed with 1L chemotherapy. Blood biomarkers associated with tumor immune gene signatures in this trial may provide mechanistic insight into the development of antitumor immunity and indicate patient subpopulations that could benefit from ICIs. We used EpiSwitch analysis of PB to identify structural-functional epigenetic changes in genomic architecture, designated chromatin conformation signatures (CCSs).

Methods

PB from 496 pts in the JAVELIN Bladder 100 trial underwent EpiSwitch analysis by PCR assay of 3D genomic templates prepared from fixed intact nuclei. Tumor immune activity was scored using a gene expression signature (JAVELIN Renal 101 Immune [JR101I]). CCS association with tumor JR101I scores was determined via univariate and multivariate analyses of a training set of 80 specimens.

Results

We identified 25 CCSs from the training set. One CCS was proximal to POU2F2, a transcription factor instrumental in B cell development. Patients whose PB lacked the POU2F2 CCS had elevated tumor JR101I scores, corresponding to increased gene expression associated with tertiary lymphoid structures (TLSs). The POU2F2 CCS may therefore influence key steps in TLS formation. In patients with a median tumor mutation burden (TMB) of ≤ 7.66 non-synonymous SNVs per Mb, the avelumab+BSC vs BSC hazard ratios in the CCS-absent subpopulation was 0.56 (95% CI, 0.32–0.96; p=0.037; n=83); and in the CCS-present population was 1.2 (95% CI, 0.83–1.75; P=0.34; n=158). CCSs affecting the ability to form TLSs may influence response to avelumab at low TMB.

Conclusions

PB CCSs may be associated with TLS, tumor JR101I scores, and the degree of OS benefit. These findings support further analysis of CCSs to assess potential clinical utility.

https://bladder.uroonco.uroweb.org/publication/genomic-biomarkers-in-peripheral-blood-pb-from-patients-pts-enrolled-in-the-javelin-bladder-100-trial-of-avelumab-first-line-1l-maintenance-in-advanced-urothelial-carcinoma-auc/

In that study, the systemic readout with the EpiSwitch 3D genomic profile far exceeded the predictive powers of the IHC PD-L1 expression in the tumour biopsy. Recently, the systemic EpiSwitch approach has also been validated on a cohort of 384 metastatic urothelial cancer patients tin a 2-arm study, from the Pfizer JAVELIN Bladder 100 trial NCT02603432 [69]. In that study, an EpiSwitch systemic biomarker associated with Altogether, our data show that the predictive model developed in this study has high biological relevance and is anchored on the baseline presence of a prevalent systemic 3D genomic profile, itself functionally linked to immuno-genetic settings conducive to the clinical outcome of response to PD-(L)1 blockade

Https://oncology.medicinematters.com/esmo-2022/urothelial-cancer/javelin-bladder-100-analysis-epigenetic-marker-avelumab/23475384

Https://www.youtube.com/watch?v=nNZEfG9u5Qs

Https://www.bupa.co.uk/business/health-insights/cancer-innovations-and-improving-outcomes