INTRODUCTION: Rapidly progressive dementias (RPDs) are a group of neurolog- ical disorders characterized by a rapid cognitive decline. The diagnostic value of blood-based biomarkers for Alzheimer’s disease (AD) in RPD has not been fully explored.
METHODS: We measured plasma brain-derived tau (BD-tau) and p-tau181 in 11 con- trols, 15 AD patients, and 33 with RPD, of which 19 were Creutzfeldt-Jakob disease (CJD).
RESULTS: Plasma BD-tau differentiated AD from RPD and controls (p = 0.002 and p = 0.03, respectively), while plasma and cerebrospinal fluid (CSF) p-tau181 distin- guished AD from RPD (p < 0.001) but not controls from RPD (p > 0.05). The correlation of CSF t-tau with plasma BD-tau was stronger (r = 0.78, p < 0.001) than the correlation of CSF and plasma p-tau181 (r = 0.26, p = 0.04). The ratio BD-tau/p-tau181 performed equivalently to the CSF t-tau/p-tau181 ratio, differentiating AD from CJD (p < 0.0001).
DISCUSSION: Plasma BD-tau and p-tau181 mimic their corresponding cerebrospinal fluid (CSF) markers. P-tau significantly increased in AD but not in RPD. Plasma BD-tau, like CSF t-tau, increases according to neurodegeneration intensity.
TR-1: Notification of major interest in shares. To download this report as a PDF file click here.
TR-1: Notification of major interest in shares. To download this report as a PDF file click here.
TR-1: Notification of major interest in shares. To download this report as a PDF file click here.
IMPORTANCE Blood-based measurements of total tau (T-tau) are commonly used to examine neuronal injury in patients with traumatic brain injury (TBI), but current assays do not differentiate between brain-derived tau (BD-tau) and tau produced in peripheral tissues. A novel assay for BD-tau has recently been reported that selectively quantifies nonphosphorylated tau of central nervous system origin in blood samples.
OBJECTIVES To examine the association of serum BD-tau with clinical outcomes in patients with severe TBI (sTBI) and its longitudinal changes over 1 year.
DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study was conducted at the neurointensive unit at the Sahlgrenska University Hospital, Gothenburg, Sweden, between September 1, 2006, and July 1, 2015. The study included 39 patients with sTBI followed up for up to 1 year. Statistical analysis was performed between October and November 2021.
EXPOSURES Serum BD-tau, T-tau, phosphorylated tau231 (p-tau231), and neurofilament light chain (NfL) measured on days 0, 7, and 365 after injury.
MAIN OUTCOMES AND MEASURES Associations of serum biomarkers with clinical outcome and longitudinal change in sTBI. Severity of sTBI was evaluated using the Glasgow Coma Scale at hospital admission, while clinical outcome was assessed with the Glasgow Outcome Scale (GOS) at 1-year follow-up. Participants were classified as having a favorable outcome (GOS score, 4-5) or unfavorable outcome (GOS score, 1-3).
RESULTS Among the 39 patients (median age at admission, 36 years [IQR, 22-54 years]; 26 men [66.7%]) in the study on day 0, the mean (SD) serum BD-tau level was higher among patients with unfavorable outcomes vs those with favorable outcomes (191.4 [190.8] pg/mL vs 75.6 [60.3] pg/mL; mean difference, 115.9 pg/mL [95% CI, 25.7-206.1 pg/mL]), while the other markers had smaller between-group mean differences (serum T-tau, 60.3 pg/mL [95% CI, −22.0 to 142.7 pg/mL]; serum p-tau231, 8.3 pg/mL [95% CI, −6.4 to 23.0 pg/mL]; serum NfL, −5.4 pg/mL [95% CI, −99.0 to 88.3 pg/mL]). Similar results were recorded on day 7. Longitudinally, baseline serum BD-tau concentrations showed slower decreases in the whole cohort (42.2% on day 7 [from 138.6 to 80.1 pg/mL] and 93.0% on day 365 [from 138.6 to 9.7 pg/mL]) compared with serum T-tau (81.5% on day 7 [from 57.3 to 10.6 pg/mL] and 99.0% on day 365 [from 57.3 to 0.6 pg/mL]) and p-tau231 (92.5% on day 7 [from 20.1 to 1.5 pg/mL] and 95.0% on day 365 [from 20.1 to 1.0 pg/mL]). These results did not change when considering clinical outcome, where T-tau decreased twice as fast as BD-tau in both groups. Similar results were obtained for p-tau231. Furthermore, the biomarker levels on day 365 were lower, compared with day 7, for BD-tau but not T-tau or p-tau231. Serum NfL had a different trajectory to the tau biomarkers, with levels increasing by 255.9% on day 7 compared with day 0 (from 86.8 to 308.9 pg/mL) but decreasing by 97.0% by day 365 vs day 7 (from 308.9 to 9.2 pg/mL).
CONCLUSIONS AND RELEVANCE This study suggests that serum BD-tau, T-tau, and p-tau231 have differential associations with clinical outcome and 1-year longitudinal change in patients with sTBI. Serum BD-tau demonstrated utility as a biomarker to monitor outcomes in sTBI and can provide valuable information regarding acute neuronal damage.
Bioventix plc
(“Bioventix” or the “Company”)
Board Appointment
Bioventix plc (BVXP), a UK company specialising in the development and commercial supply of high-affinity monoclonal antibodies for applications in clinical diagnostics is delighted to announce that it has appointed Joanne (Jo) Pisani to the Board, as an independent Non-Executive Director, with immediate effect. Jo will chair the Company’s Audit Committee.
Jo is a chartered engineer with a distinguished background in the Pharmaceutical, Life Sciences and Biotech sectors. She has held roles at GSK and BP in strategy, commercial and operational functions before working in strategic consultancy. She led PwC’s UK Pharmaceutical and Life Sciences practice, assisting clients with developing strategy, designing and implementing transformational change and completing M&A transactions.
Jo is a passionate supporter of critical public health issues, such as tackling dementia, rare diseases and anti-microbial resistance. She focuses on supporting charities, universities and business start-ups. She is chair of Birmingham’s Precision Health Technology Accelerator and also chairs the Advisory Board for London’s MedCity. She serves on the boards of the UK Dementia Research Institute, LifeArc, The RSA Group, London and Partners and Beacon. She is also a Non-Executive Director and strategic advisor to biotech companies in the UK, Finland and Spain
Ian Nicholson, Chairman, commented: “The Board is delighted to welcome Jo to Bioventix. She brings considerable leadership and strategic experience in Life Sciences and biotech businesses, large and small, that is highly relevant to Bioventix and the opportunities being addressed by the Company. I am confident that she will add considerable value to the Company.”
For further information please contact:
| Bioventix plc
Peter Harrison Bruce Hiscock |
Chief Executive Officer Chief Financial Officer |
Tel: 01252 728 001 |
| finnCap Ltd
Geoff Nash/Simon Hicks Alice Lane |
Corporate Finance ECM |
Tel: 020 7220 0500 |
Regulatory disclosures
INFORMATION REQUIRED UNDER RULE 17 AND SCHEDULE 2, PARAGRAPH (G) OF THE AIM RULES FOR COMPANIES (“AIM RULES”)
| Full name: | Joanne (Jo) Patra Pisani |
| Age: | 58 |
| Shareholding in the Company: | No shares held |
| Current directorships and partnerships: |
UK DRI Ltd Beacon: for rare diseases Ltd LAM Action LifeArc London & Partners Limited PHTA Ltd Ostique Limited Adora Digital Health Ltd Elem Biotech SL Aplagon Oy RSA (Holdings) Ltd MedCity Ltd
|
| Historic directorships and partnerships in previous 5 years: | Karoo CGT Limited
Pricewaterhouse Coopers LLP |
There is no further information to be disclosed in relation to the director appointment pursuant to Rule 17 and Schedule 2, paragraph (g) of the AIM Rules.
Bioventix plc
(“Bioventix” or the “Company”)
Director/PDMR Shareholdings and Issue of Equity
Bioventix plc (BVXP), a UK company specialising in the development and commercial supply of high-affinity monoclonal antibodies for applications in clinical diagnostics, was notified on 18 May 2023 of the following transactions in its ordinary shares of 5 pence each (“Ordinary Shares”):
|
Director |
Role |
Options over Ordinary Shares exercised |
Ordinary Shares sold |
Average sale price per Ordinary Share |
Ordinary Shares subsequently held |
Percentage of issued share capital subsequently held |
|
Ian Nicholson |
Non-Executive Chairman |
1,638 |
1,638 |
3,651.53 |
13,000 |
0.2% |
The options over Ordinary Shares (“Options”) were exercised at a price of 1350 pence per Ordinary Share pursuant to the Company’s 2013 EMI Share Option Scheme, details of which can be found at www.bioventix.com. In addition, a current employee exercised 2,333 Options.
Issue of Equity
The Company has applied for 3,971 new Ordinary Shares to be admitted to trading on AIM (“Admission”). It is expected that Admission will occur and that dealings will commence in the new Ordinary Shares on 25 May 2023. The new Ordinary Shares will rank pari passu with the existing Ordinary Shares.
The total number of Ordinary Shares in issue following Admission will be 5,219,656 and the Company holds no shares in treasury. Therefore, the total number of Ordinary Shares with voting rights in the Company will be 5,219,656.
The above figure of 5,219,656 may be used by shareholders as the denominator for the calculations by which they will determine if they are required to notify their interest in, or a change to their interest in, Bioventix under the FCA’s Disclosure Guidance and Transparency Rules.
For further information please contact:
|
Bioventix plc Peter Harrison Bruce Hiscock |
Chief Executive Officer Chief Financial Officer |
Tel: 01252 728 001 |
|
finnCap Ltd Geoff Nash/Simon Hicks Alice Lane |
Corporate Finance ECM |
Tel: 020 7220 0500 |
Notification and public disclosure of transactions by persons discharging managerial responsibilities and persons closely associated with them
|
1 |
Details of the person discharging managerial responsibilities (“PDMR”) / person closely associated (“PCA”) |
|||||
|
a) |
Name |
Ian Nicholson |
||||
|
2. |
Reason for the Notification |
|||||
|
a) |
Position/status |
Chairman |
||||
|
b) |
Initial notification/Amendment |
Initial notification |
||||
|
3. |
Details of the issuer, emission allowance market participant, auction platform, auctioneer or auction monitor |
|||||
|
a) |
Name |
Bioventix plc |
||||
|
b) |
LEI |
213800225MHX7LZQY108 |
||||
|
4. |
Details of the transaction(s): section to be repeated for (i) each type of instrument; (ii) each type of transaction; (iii) each date; and (iv) each place where transactions have been conducted |
|||||
|
a) |
Description of the Financial instrument, type of instrument |
Ordinary Shares of 5 pence each |
||||
|
Identification code |
GB00B4QVDF07 |
|||||
|
b) |
Nature of the transaction |
Exercise of Options over Ordinary Shares |
||||
|
c) |
Price(s) and volume(s) |
|
||||
|
d) |
Aggregated information: · Aggregated volume · Price |
See 4(c) |
||||
|
e) |
Date of the transaction |
18 May 2023 |
||||
|
f) |
Place of the transaction |
Off market transaction |
||||
|
1 |
Details of the person discharging managerial responsibilities (“PDMR”) / person closely associated (“PCA”) |
|||||
|
a) |
Name |
Ian Nicholson |
||||
|
2. |
Reason for the Notification |
|||||
|
a) |
Position/status |
Chairman |
||||
|
b) |
Initial notification/Amendment |
Initial notification |
||||
|
3. |
Details of the issuer, emission allowance market participant, auction platform, auctioneer or auction monitor |
|||||
|
a) |
Name |
Bioventix plc |
||||
|
b) |
LEI |
213800225MHX7LZQY108 |
||||
|
4. |
Details of the transaction(s): section to be repeated for (i) each type of instrument; (ii) each type of transaction; (iii) each date; and (iv) each place where transactions have been conducted |
|||||
|
a) |
Description of the Financial instrument, type of instrument |
Ordinary Shares of 5 pence each |
||||
|
Identification code |
GB00B4QVDF07 |
|||||
|
b) |
Nature of the transaction |
Sale of Ordinary Shares |
||||
|
c) |
Price(s) and volume(s) |
|
||||
|
d) |
Aggregated information: · Aggregated volume · Price |
See 4(c) |
||||
|
e) |
Date of the transaction |
18 May 2023 |
||||
|
f) |
Place of the transaction |
London Stock Exchange, AIM Market (XLON)
|
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INTRODUCTION: We investigated the effects of matrix type and reagent batch changes on diagnostic performances and longitudinal trajectories of brain-derived tau (BD-tau).
METHODS: We evaluated (i) Cohort 1: paired EDTA plasma and serum from Alzheimer biomarker-positive older adults versus controls (n = 26); and (ii) Cohort 2: n = 79 acute ischemic stroke patients with 265 longitudinal samples across four time points. RESULTS: In Cohort 1, plasma and serum BD-tau were strongly correlated (rho = 0.96, p < 0.0001) with similar diagnostic performances (AUCs >99%) and correlations with CSF total-tau (rho = 0.93–0.94, p < 0.0001). However, absolute concentrations were ∼40% higher in plasma versus serum. In Cohort 2, first and repeated BD-tau measurements showed a near-perfect correlation (rho = 0.96, p < 0.0001), with no significant between-batch concentration differences. In longitudinal analyses, sub- stituting ∼10% of the first-run concentrations for the remeasured values showed overlapping estimated trajectories without significant differences at any time point.
RESULTS: In Cohort 1, plasma and serum BD-tau were strongly correlated (rho = 0.96, p < 0.0001) with similar diagnostic performances (AUCs >99%) and correlations with CSF total-tau (rho = 0.93–0.94, p < 0.0001). However, absolute concentrations were ∼40% higher in plasma versus serum. In Cohort 2, first and repeated BD-tau measurements showed a near-perfect correlation (rho = 0.96, p < 0.0001), with no significant between-batch concentration differences. In longitudinal analyses, substituting ∼10% of the first-run concentrations for the remeasured values showed overlapping estimated trajectories without significant differences at any time point.
DISCUSSION: BD-tau has equivalent diagnostic accuracies, but non-interchangeable absolute concentrations, in plasma versus serum. Furthermore, the analytical robustness is unaffected by batch-to-batch reagent variations.
Bioventix plc
(“Bioventix” or “the Company”)
Director Dealing
Bioventix plc (BVXP), a UK company specialising in the development and commercial supply of high-affinity monoclonal antibodies for applications in clinical diagnostics, announces that the Company was notified on 24 April 2023 that on 24 April 2023 Bruce Hiscock, Chief Financial Officer of the Company, purchased a total of 11 ordinary shares of 5 pence each in the Company (“Ordinary Shares”), at an average price of 3,823 pence per Ordinary Share (the “Purchase”). The Ordinary Shares were purchased under a dividend reinvestment plan (“DRIP”).
Following the Purchase, Bruce Hiscock has a beneficial interest in 761 Ordinary Shares, representing approximately 0.01 per cent. of the issued share capital of the Company.
The notification below, made in accordance with the requirements of the EU Market Abuse Regulation, provides further details.
For further information please contact:
|
Bioventix plc Peter Harrison |
Chief Executive Officer |
Tel: 01252 728 001 |
|
finnCap Ltd Geoff Nash/Simon Hicks Alice Lane |
Corporate Finance ECM |
Tel: 020 7220 0500 |
Notification and public disclosure of transactions by persons discharging managerial responsibilities and persons closely associated with them
|
1 |
Details of the person discharging managerial responsibilities / person closely associated |
|
|
a) |
Name |
Bruce Hiscock |
|
2. |
Reason for the Notification |
|
|
a) |
Position/status |
Chief Financial Officer |
|
b) |
Initial notification/Amendment |
Initial notification |
|
3. |
Details of the issuer, emission allowance market participant, auction platform, auctioneer or auction monitor |
|
|
a) |
Name |
Bioventix Plc |
|
b) |
LEI |
213800225MHX7LZQY108 |
|
4. |
Details of the transaction(s): section to be repeated for (i) each type of instrument; (ii) each type of transaction; (iii) each date; and (iv) each place where transactions have been conducted |
|
|
a) |
Description of the Financial instrument, type of instrument |
Ordinary Shares of 5 pence each |
|
Identification code |
GB00B4QVDF07 |
|
|
b) |
Nature of the transaction |
Purchase of Ordinary Shares |
|
c) |
Price(s) and volume(s) |
11 Ordinary Shares 3,823 pence |
|
d) |
Aggregated information:
· Aggregated volume
· Price |
Purchase of 11 Ordinary Shares at 3,823 pence each |
|
e) |
Date of the transaction |
24 April 2023 |
|
f) |
Place of the transaction |
London Stock Exchange, AIM Market (XLON) |
TR-1: Notification of major interest in shares. To download this report as a PDF file click here.