AroCell AB ja TK1-testi

Subwaymap - this may be the latest official overview of all assays available on Roche cobas (last update 2020).

Source (pdf download):

Wow - what a complicated graphic design! All those interconnections between all these different areas of application! And if TK1 is to be added, that would bring even more complexity to that graphic design, with several new interconnections to that subwaymap (ex between oncology, infection and womens health).

With all these many, many assays available on Roche cobas - why shouldn´t TK1 become a part of this?

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Interesting recently published results on sTK1p in combination with CA15-3 in breast cancer, non-metastatic settings. Seems to associate to earlier results from AroCell which also showed benefit in combining TK1 and CA15-3 in breast cancer.

These new results are also based on measurements of serum TK1 protein, but the article does not specify which TK1-ELISA that is used.

“In the present study, the combination of TK-1 and CA 15-3 biomarkers raised the sensitivity from 90% and 88%, respectively, to 98%. Consequently, the results of this study clearly imply that a combination of TK-1 ELISA and CA 15-3 will be extremely useful, as the two tests appear to provide complementary information.”

Source (published June 2022):
https://www.researchgate.net/publication/361788125_Evaluation_of_Thymidine_Kinase-1_as_a_potential_biomarker_and_its_association_with_CA_15-3_in_patients_with_non-metastatic_breast_cancer

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Some amateur speculations on the Rhovac drug candidate, the cancervaccin RV001V, that recently failed in phase II. Just speculations…

As I understand… initially RV001V activates the bodys immune system to recognize “RHOC”, which is a protein only present on migrating cancercells. The goal is to eliminate migrating cancercells and thereby reduce/eliminate the occurrence of metastasis.
Source: RV001 - vetenskapligt koncept | RhoVac AB

Ok… but what, more precisely, is the meaning of the term “migrating”, in the Rhovac concept?

If I, as an amateur, were to guess… it would be clear that “migrating cancercells” of course includes such RHOC-presenting cancercells that (i) have left the primary tumor and are free circulating, perhaps in the blood. Probably “migrating cancercells” would also (ii) refer to such RHOC-presenting cancercells that are still within the primary tumor, not yet released?

But… what about a case when (iii) a distant metastas have allready been established? Does the action of RV001V also reach such “migrating cancercells” that have allready established a new and emerging metastas?

If NOT… if RV001V is NOT able to target allready established metastases… then it is perhaps logical (?) that the status of such allready established metastasis at the defined time for biochemical recurrence could be a highly relevant factor? With the potential to have effect on the outcome of the study?

So, what were the criteria for measuring new metastasis in the failed Rhovac study? The study protocol says that among the inclusion criteria were:
“Biochemical recurrence (BCR) within 3 years of radical prostatectomy (RP) or definitive RT and no distant metastasis by standard CT imaging and bone scintigraphy, or locoregional recurrence (including lymph nodes) assessed by CT or multi-parametric magnetic resonance imaging (MRI) and confirmed with negative biopsy in case of prior RT.”
Source: Study of RV001V in Biochemical Failure Following Curatively Intended Therapy For Localized Prostate Cancer - Full Text View - ClinicalTrials.gov

Ok… as I understand, the failed Rhovac study used CT imaging to define if distant metastasis had occurred at the time of biochemical recurrence. But… what if CT imaging is not sensitive enough to capture very small and emerging metastasis? What if there were a way to complement CT imaging, complement the information regarding possible metastases, and thereby be able to more precisely define differentiated patient populations at the time for biochemical recurrence?

And the term “biochemical recurrence” is also interesting. In the Rovac prostate study, the definition appears to be connected to the “doubling time” of defined levels of PSA.

The doubling time of PSA is also closely related to the primary outcome in the Rhovac study. But what if there are emerging metastasis unnoticed by CT imaging at the time for biochemical recurrence? As I understand, such distant metastasis outside of the prostate, will not generate any increasing PSA? And, if so, they will have no impact on the defined primary outcome of the study protocol?

In Per Olof Lundgrens 30-year study, the authors define some areas where TK1 could become useful, including:
“A possible area of use is the evaluation of the probability of metastatic disease at the time of biochemical recurrence.”
Source: https://onlinelibrary.wiley.com/doi/full/10.1002/pros.24335

As I understand, Per Olof Lundgrens study (published March 2022) is the first study from “the AroCell sphere” to mention the term “biochemical recurrence”.
And exactly this… “evaluation of the probability of metastatic disease at the time of biochemical recurrence” (from the Lundgren study) could, as I would like to propose :slight_smile:, perhaps be a possible key-factor in the Rhovac case. Also noticeable is Per Anders Abrahamssons former role as a scientific adviser to Rhovac.

Of course, as an amateur I don´t understand these things… but sometimes it is interesting just to try and follow the “logic”… :slight_smile: Just speculations. Maybe its all wrong… very wrong…

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Speculations on the formal endpoints of different assays measuring levels of TK1 in serum.

When comparing DiviTum (Biovica), TK-LIAISON (Diasorin) and TK 210 ELISA (AroCell), the initial layman approach is often to notice the differences between the assays - with the DiviTum and TK-LIAISON assays measuring activity of the enzyme, whilst TK 210 ELISA measures the amount of the protein in the sample.

That approach seems to, of course, be relevant… but from a strict and formal “FDA-regulatory” perspective it may perhaps also be of interest to notice similarities between the assays?

One such approach could be to appreciate that all the assays (DiviTum, TK-LIAISON and TK 210 ELISA) can be defined as measuring LEVELS of the TK1 enzyme. In fact, when looking at the different protocols of the assays, it seems as if the formal endpoints of the assays are quite similar!

Starting with the endpoint of (1) AroCell TK 210 ELISA - this is clearly a quantitative measurement describing the concentration of the protein in the sample. And when (2) looking at the protocol of the TK-LIAISON assay, the formal endpoint is U/L… and this is in fact, formally speaking, also a quantitative measurement! This means that the endpoint of the TK-LIAISON assay, in fact similarly to TK 210 ELISA, appears to be describing a supposed concentration, or a quantity! And, similarly, (3) in the case of DiviTum there seems also to be a quantitative endpoint of the assay (Du/L)!

Thus, comparing the different assays from a strictly formal viewpoint, it may be a case that all three assays deliver an endpoint describing a quantitative measurement!

And, looking at the different assays from such a strictly formal perspective it may be the case that the question of measurement via “activity versus protein” can, in fact, be reduced to just a preferred “method of choice” leading to the very same formal endpoint status - which is a quantitative measurement!

Looking at the endpoints of the assays from such a perspective… if the DiviTum and TK-LIAISON assays where to be defined as to, formally speaking, differ significantly from TK 210 ELISA, shouldn´t that require a change of the definition of the endpoints of the DiviTum and TK-LIAISON assays?

An assay endpoint describing the workload performed by the TK1-enzyme, such as processed units per time intervall, would differ from TK 210 ELISA. But this is not the case in the protocols of either the DiviTum or the TK-LIAISON assays, both having a quantitative endpoint - which, similarly to TK 210 ELISA, describe a quantity, or a concentration of the enzyme.

This is of course all amateur speculations… but if such a formal perspective on the assay-endpoints is relevant… it may perhaps have implications on future FDA approaches…?

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Onko Hultman siirtänyt omistuksensa erillisen yhtiön nimiin, ja onko sillä edes mitään merkitystä?

Skepparhagen AB

Anders has always made his ownership transactions through his private company - Skepparhagen AB. So… no, this is not in any way a new approach. Hopefully there are good news building up in pipeline… :slight_smile:

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The upcoming ISOBM congress, 13th - 17th October, may be interesting as it this year appears to be a lot of focus on biomarkers in prostate cancer and bladder cancer. As AroCells serum TK1 biomarker have allready shown very promising results in prostate cancer - for example (i) in connection with Prostate Health Index (PHI), (ii) an AroCell patent application within metastatic prostate cancer, and (iii) most lately results from the unique 30 year followup study in prostate cancer - this congress may perhaps be an interesting forum for AroCell??

Also there seems to allready be a planned lecture with Thorsten Ecke on new development for the UBC-rapid test in bladder cancer!

Thorsten Ecke; BTA stat, NMP22, UBC rapid test, UBC rapid visual, and uromonitor as tumour marker for urinary bladder cancer: interim results of a german multicentre-study”

I am not at all sure… but wasn´t one possible goal of the “german multicentre-study” to maybe be able to generate data enabling inclusion of the UBC-test in german guidelines in bladder cancer??

Maybe of interest is also noticing the names of Thorsten Ecke and Josko Osredkar in the Board of Directors of the congress, and Vivian Barak as participating in one of the planned lectures (Osredkar and Barak has previously participated and contributed to research and development on the TK1 biomarker).

Source (planned lectures):
https://www.isobm2022.net/lecturers/

Source (ISOBM Board of Directors):
https://www.isobm.org/about-isobm/board/

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The AroCell US patent application “Respiratory infection detection and classification” has recently been published (14 July) and seems to be on track. Inventors of this patent application are Staffan Eriksson and Per Venge. US20220221456 RESPIRATORY INFECTION DETECTION AND CLASSIFICATION

Another very interesting biomarker in connection with TK1 in this area (bacteria, virus, mycoplasma) is HNL (another name is NGAL) which has been extensively researched by Per Venge, who seems to have several collaborations in this area (ref; see forum post 15 feb), among them the UK based company Ag Plus Diagnostics (Per Venge in the management team and/or in the board of directors).

Maybe it is of some interest to follow some links that may indicate AG Plus Diagnostics as an important collaboration partner to Per Venge? Apparently Per Venge also have other patents, as this patent through a company named Future Medical Diagnostics: WO2020035028 DETECTION OF INFECTION

This company, "Future Medical Diagnostics", seems to be identical to a Chineese Company “Suzhou Fenrui Medical Diagnostic Technology Co., Ltd” (according to a “google translate” of the Chineese company name, in the same patent application as above; 苏州芬瑞医疗诊断科技有限公司 ). WO2020035028 DETECTION OF INFECTION

And one of the major shareholders in “AG Plus Diagnostics” seems to be precisely this company - “Suzhou Fenrui Medical Diagnostic Technology Co., Ltd”. Agplus Holdings Limited - Company Profile - Pomanda

So, this may indicate (?) a link between Per Venges WO-patent (as an inventor on a panel of biomarkers enabling the possibility to distinguish between a bacterial or a virus infection) and the UK based company AG Plus Diagnostics. As I understand, it is precisely this panel of biomarkers that forms the basis of the very interesting expanded study including also TK1 (which, as I understand, also adds the ability for this expanded panel of biomarkers to more clearly distinguish between bacteria/virus and mycoplasma infection). HNL (Human Neutrophil Lipocalin) and a multimarker approach to the distinction between bacterial and viral infections - ScienceDirect

Maybe this on Per Venge and AG Plus is of some interest, I dont know… after all, the EU recognition of HNL (2017) and the impressive research and discoveries done by Per Venge are facts.

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The Diasorin patents on the TK-activity assay “TK-LIAISON” will expire this month (July 2022) according to the following links.

https://patents.google.com/patent/EP1385005B1/en
https://patents.google.com/patent/DE60217665T2/en

Inventors of this assay, which measures TK1-activity, are Staffan Eriksson and Anders Öhrvik.

From my amateur perspective, I find it relevant to ask why TK-LIAISON should not be able to deliver the same clinical utility as the DiviTum TK-activity assay, in the area of CDK4/6-inhibitors, used in advanced metastatic cancer disease??

And a combination assay, TK 210 ELISA combined with TK-LIAISON, would maybe perform even better?

Is such a combination assay a possibility?? Is it possible to combine TK 210 ELISA and TK-LIAISON into one single assay?? If possible, this would create an assay measuring both TK1-protein and activity at the same time.

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A reminder of this external study (2021) on sTK1p in prostate cancer, which delivers very interesting and positive results in prostate cancer. Not least the results in the critical gray-zone, 4-10 ng/ml, seems very interesting in connection to screening and the problematic overuse of biopsies.

https://medicopublication.com/index.php/ijfmt/article/view/16939/15022

In my view, Henrik Grönberg now simply have to acknowledge sTK1p as a potential additional resource to the Sthlm3-test. :slight_smile:

Why isn´t sTK1p allready signed in to the Sthlm3-test?? Is it due to some kind of “internal academic prestige”?? Competing research groups… with a political mindset determined to not in any way recognize the benefits of any external complementary approach to eventual upcoming Swedish prostate cancer screening?

In my view it is absolutely clear and mandatory that serum TK1 concentration must be recognized and included in upcoming studies on Swedish prostate cancer screening, for example with regard to the grey zone 4-10 ng/ml. Why isn´t anyone talking about these benefits? Why is there no studies with TK 210 ELISA on this subject?

And why is there no results published with TK 210 ELISA and CDK4/6-inhibitors? I´ve got the feeling that AroCell deliberately is holding back results and development. Why? Perhaps a “behind-the-scene” deal with Biovica not to interfere in the area of CDK4/6-inhibitors? What else could be the reason for AroCell holding back?

Ok, maybe AroCells upcoming combination test, TK1+cytokeratin, will perform even better than TK1 alone? Still, if you never act strongly on obvious benefits using sTK1p, than nothing will happen, ever.

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Tubex on instagram… nice pictures, maybe generated from Indonesia?
https://www.instagram.com/tubextf/

According to earlier press releases from IDL Biotech, it seems as if AroCell/IDL have reached distribution agreements for TUBEX TF in the following countries:

Indonesia, Nepal, Bhutan, Malaysia, Kenya, Uganda, Zimbabwe, Rwanda, South Sudan, Somalia, Ghana

Sources (press releases, Tubex distribution agreements):

2019-10-21 Indonesia IDL Biotech byter distributör i Indonesien - IDL Biotech

2019-11-04 Nepal, Bhutan IDL Biotech tecknar distributionsavtal i Asien - IDL Biotech

2019-11-04 Kenya Nyhetsartikel | Spotlight

2019-11-26 Uganda Nyhetsartikel | Spotlight

2019-12-05 Malaysia Nyhetsartikel | Spotlight

2020-03-13 Zimbabwe Nyhetsartikel | Spotlight

2021-01-22 Rwanda, South Sudan, Somalia IDL Biotech signerar distributörsavtal i Rwanda, Sydsudan och Somalia - IDL Biotech

2021-03-03 Ghana IDL Biotech signerar distributörsavtal i Ghana. - IDL Biotech

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On tämä kyllä mielenkiintoinen sijoitus:

TJ ostanut, omistaa 1M osaketta

Neuvotellaan Attanan kanssa sopimusvalmistuksesta

P/B 0,5

FDA ?

Monta erilaista hanketta vireillä

Anti läpi 0,75

Pienellä vaihdolla osaketta myydään 0,5

Isommat ei kuitenkaan ole lähteneyt myymään

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Biovica receives FDA approval for DiviTum®TKa.

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So now AroCell could use it as a predicate device for a partial implementation 510k of TK210. I wonder if that’s what they will do, or are they still going for the De Novo application…

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Jossain vaiheessa oli jittua että, seuraavat noiden hyväksyntöjen etenemistä tarkkaan.

Ymmärsin että siitä olisi hyötyä myös Arocelin tilanteeseen, joten odottavaisin mielin.

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According to FDAs official classification register, it seems as if DiviTum have been coupled to a predicate device related to cytokeratin fragments.

“Device Classsification Name: cytokeratin fragments 21-1 eia kit”
Source: 510(k) Premarket Notification

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DiviTum is now FDA-cleared for use within monitoring of metastatic breast cancer… so the use of a predicate device specified to be used within lungcancer, was, apparently (?), not a hindrance in the case of the DiviTum clearance?!

“The CYFRA 21-1 EIA kit is intended for the quantitative determination of soluble cytokeratin 19 fragments in human serum. The assay is to be used as an aid in monitoring disease progression during the course of disease and treatment in lung cancer patients. Serial testing for patient CYFRA 21-1 assay values should be used in conjunction with other clinical methods used for monitoring lung cancer.”

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=K202852
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm?id=3198

So… apparently a use within lungcancer can serve as predicate device for a use within breast cancer??
Hmm… but than…why shouldn´t the situation be similar in the case of the same cytokeratin kit (as predicate) visavi prostate cancer?

Maybe TK 210 ELISA can use the same cytokeratin kit as a predicate device for 510k applications within both (1) monitoring of breast cancer and (2) monitoring of prostate cancer?

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Quote from an analyst update on Biovica, published today by RedEye:

“The current market value of USD <90m for a company with FDA approval is hugely undemanding.”

Ok, so a market value of USD <90m for a company with FDA approval is hugely undemanding.

AroCell currently have a valuation less than USD 13m. The company will probably have the opportunity to file not only one (1), but potentially at least three (3) FDA 510k applications in the coming 1-2 years.

  1. UBD Rapid (an indication within bladder cancer)
  2. TK 210 ELISA (an indication within breast cancer)
  3. TK 210 ELISA (an indication within prostate cancer)

But as always… when it comes to company valuation… Biovica and AroCell does not seem to play by the same set of rules. Why is that?

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There was some discussion about that in this thread, back in 2020 or so. The consensus seemed to be that Biovica is far superior in marketing capabilities, while AroCell’s marketing is lower quality than “market average”.

Product-wise, AroCell is more capable, while Biovica’s product line is more, let’s say focused.

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AroCell and Diasorin are mentioned by name in a recent article (published 2022-08-01) on Biovicas FDA clearence. Quotes from the article:

"In a 2021 research note, Pareto Securities analyst Dan Akshuti noted it currently has little or no direct competition. “With the exceptions of Arocell and Diasorin, we have not found any companies that have clinically evaluated their products. All of the companies observed sell their products for research use only,” wrote Akshuti.”

“Costs for the kits vary enormously /…/ and due to non-clinically validated regulatory approval in any kind of indication, we do not consider the kits as competitors to Divitum."

Ok, fine. Congratulations - Biovica has no competitor. Good luck shipping hemolyzed blooddraws all around the US.

Link to the article:

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