The Questionable Ethics of Anisina

I really appreciate the value that many of the Long Tail readers bring to this site, and I’d particularly like to thank a couple of followers that sent me (both publicly and privately) the link to the Kids’ Cancer Project website that talks about Anisina (I have also take a PDF of it in case the page(s) gets taken down or modified).

You will note that I touch on the ethics of the biotechnology industry very often in this forum because it is a constant challenge and a constant facet of drug development that executives need to consider every day. Issues of disclosure, transparency, data manipulation/abbreviation and corporate governance are so much greater in this field, simply because of the nature of what we do and the capital at risk. Sometimes the ethics of conducting a bioscience business doesn’t just extend to the obvious stakeholders like shareholders and patients, but also the wider community.

I was highly concerned to read this website because it is asking the public for donations to support the clinical development of Anisina, but has no mention whatsoever of Novogen (ASX : NRT), or Peter Gunning’s involvement in Novogen (at the time of writing this post, he is a director). How can you solicit public donations for clinical development of a drug owned by a (comparatively) well-capitalised public company, going through all sorts of corporate governance challenges no less, and not share that information with a prospective donor? Even Gunning’s biography page (PDF here again) doesn’t mention Novogen or – to be specific – the research and financial conflict of interest that Peter Gunning has with an ASX-list company is not disclosed (not even in the “governance” pagesPDF).

My readers inform me that Novogen used to be mentioned on these pages. If someone has a screen snapshot, please feel free to email it to me and I will post it up. The fact that Novogen is no longer mentioned raises a red flag for me, and should be considered by shareholders to be additional evidence that the company is perhaps not tracking the way it should be with respect to its clinical programs. As one of my readers commented:

Had a phone call today from the kids cancer council, to whom I make regular donations. The interesting thing is that they were asking for an extra donation to support a new drug trial at Westmead Children’s Hospital next year, using an experimental drug called Anisina. How come Novogen isn’t funding these trials, especially since they have so much cash in reserve?

Very concerning indeed, and an excellent point. Perhaps the answer actually lies on the funding web page itself, with this soundbite courtesy of Peter Gunning :

Only the Kids’ Cancer Project was prepared to fund such progressive research into drug development.

So I guess the $40-ish million in Novogen’s bank account doesn’t count?

Aside from the questionable optics, the real issue here is that the average person who lands on this colourful and appealing site, seeing “great research” being done for childhood cancer, will have no idea of the conflicts of interest around the clinical programs they may choose to support. Frankly, I didn’t much like the content of the Anisina page either, in my view it lacks the sort of clinical measure and caution that is needed for public biomedical communication, particularly for something emotive like kids’ cancer. In my opinion it considerably oversells the impact of the research (especially considering the dearth of peer-reviewed publication around the Anisina technology).

This is unacceptable and the relationship with Novogen needs to be clearly disclosed. Fix it, please.

 

28 thoughts on “The Questionable Ethics of Anisina

  1. Just to add to that – kids cancer project have not listed Novogen in their “Proudly Supporting” section

    Novogen is mentioned but to find them you need to:

    1. http://www.thekidscancerproject.org.au/Home.aspx
    2. Click on “RESEARCH” and to the drop down “DRUG DISCOVERY ANISINA” http://www.thekidscancerproject.org.au/Research/Drug-Discovery-Anisina.aspx
    3. then scroll down to bottom of page to “Drug Discovery Program” – http://www.thekidscancerproject.org.au/Research/drug-discovery-project.aspx
    4. then scroll down to the link “Children’s Oncology Research Alliance” – http://www.childrensoncologydrugalliance.org/
    and finally you can find mention of Novogen.

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  2. The non disclosure and the seeming impropriety is staggering, worthy of a Michael West article. Surely the http://www.thekidscancerproject.org.au/has to be held to account as well and not just Novogen.

    I notice in their 2104 financial http://www.thekidscancerproject.org.au/Files/Accounts/TKCP-Signed-Financials-2014.aspx, they had $15 million income from raffles merchandise and donations.Expenses were a mighty 11 million, (if you count the “research funding and governance” which is vague)

    A nice wicket for someone.

    Your actual donation is only about 40 cents in every dollar.

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    • Well, I suppose the purpose of the charity is to fund medical research, so you want that. But yes, the responsibility for ethical disclosure is on both sides. The nexus, however, is Peter Gunning. This is something he should be showing to the public that he is “on top of”.

      I don’t, incidentally, have a problem with a company and a charity working together. It happens all the time. But there has to be transparency and justification for the use of donated funds and in the case of Novogen I struggle to see their justification to exist, let alone tap into the generosity of donors.

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  3. I think the argument being made is that there is a market failure to develop cancer drugs for children. Or at least a significant time lag between when new drugs are approved for adults then gain approval for pediatric use.

    And so by donating you might be helping bring on a new drug more quickly for children.

    You would like to think that when public monies are raised in this way then a public benefit or payoff is achieved. So for example were the drugs successful then they would be provided “free” to Australian children for example.

    The charity has raised many millions from the public and the charity has supported around a dozen or so cancer projects. How were those projects selected? Was there a competitive open peer review?

    It can’t really just be that a professor is mates with a very motivated, energetic good Samaritan so that the charity funnels money into supporting the work of a private company where the professor has an interest.

    Because this company like most micro-cap biotechs is propped up by pumps and dumps through our markets. In this case mysterious Canadian based hedge funds into unsuspecting Nasdaq punters. Which then snare ASX punters through market asymmetries between our respective markets (we can’t short sell), all facilitated by another charismatic professor who is good with social media (HC) but who now has taken garden leave (after selling a few shares).

    None of this can be true. Its just too bizarre to think that your Australian charitable children’s cancer dollar ends up supporting the lifestyle of a US / Canadian hedge fund CEO. Who most of us would have on the bottom of the list as deserving of our help.

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    • That’s a fairly nefarious analysis – but to a large extent it is true. I personally believe that there is a strong value in public-private partnerships for developing new drugs, but not when the “private” disproportionately benefits from the public. I think that charitable organisations can do a lot to make drugs available but a greater degree of sensitive is required from the corporate side when those partnerships are put in place.

      A greater degree of transparency too.

      For the big problem with the Anisina project is there is bugger all evidence that it does anything useful, and some evidence that Prof. Gunning doesn’t actually understand what he has. So then why is the public being asked to get behind it? I want to see the public get behind real science that is going to move the needle, not the quasi-science of a mediocre ASX-listed company.

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  4. I’m a little confused now about the lineage of “Anisina” in the Kids Cancer Project annual Report for 2011-2012 on page 12 under the heading: Drug Discovery Project – Professor Peter Gunning UNSW. Towards the end it speaks of them having “5” drug candidates and they expected to enter Phase 1 clinical trials in 2013. http://issuu.com/thekidscancerproject/docs/tkcp-6-032_annual_report_final

    Move forward to October 2013 when Novogen took over the “ATM” development in 2013:

    ASX RELEASE
    ============
    “Novogen acquires new technology to add to its oncology drug pipeline”
    “9 October 2013, Sydney Australia: Novogen Limited (ASX:NRT) has acquired a novel drug technology that will be developed as a potentially major class of cancer drugs known as anti-tropomyosins (anti-Tms). Anti-Tm drugs will join the Company’s growing pipeline of super-benzopyran drugs, including Trilexium and related analogs.”

    Move forward to late November 2014 and Novogen release:

    ASX RELEASE
    ============

    21 November 2014
    “NOVOGEN ANNOUNCES IDENTIFICATION OF LEAD ATM DRUG CANDIDATE”
    “Novogen today announced that it has identified its lead anti-tropomyosin (ATM) drug
    candidate. This follows the announcement on 12 November at the 2014 Annual
    General Meeting that the Company had refined its search to “5” candidate compounds
    with the final selection imminent. The final selection was confirmed yesterday with the
    Company confident that it has developed a major new initiative in the field of
    chemotherapy.”

    “ATM-3507 was designed by a team of Novogen chemists led by Dr Andrew Heaton, Novogen Vice-
    President of Drug Discovery and Manufacture.”

    “Professor Peter Gunning, Non-Executive Director of Novogen, and inventor of the ATM drug technology,
    said, “The original impetus for the ATM drug technology was the need to find more effective and safer
    therapies for pediatric cancers. Walking through the cancer ward in a children’s hospital is a powerful
    incentive to improve the health of children with cancer. To finally have the drug that we are confident of
    taking into the clinic brings this dream within sight.”

    ATM-3507 has been given the name Anisina, Turkish word for ‘in memory of’

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  5. I thought I had – Gunning is closely linked to the kids cancer project who used to be something like the oncology children’s foundation – Genscreen took some type of interest in the program back in September 2005 & called it the Trobio project – http://www.genscreen.com.au/17th-september-2005#more-9

    In August 2009 Genscreen are updating work on this Trobio project with compounds called TR400, TR500, TR600
    http://www.genscreen.com.au/august-2009

    In December 2009 Genscreen announce “TR400 has been tested in 2-D & 3-D melanoma models and in animal model of cancer” – http://www.genscreen.com.au/december-2009

    In Jan 2010 Genscreen announce “Genscreen is presently having TR400 drugs sythesised by a contractor. It is anticipated that screening results will be ready for review by March 2010. TR400 is the development lead series of Trobio project, a project within the portfolio of Genscreen Pty Ltd.
    Two other development series are also under development for complementary applications – TR500 and TR600. The intention is to outlicense TR400 as soon as a suitable partner can be found.

    2010-11 kids cancer project (oncology children’s project) in their annual report already have Gunning talking of having 5 compounds developed.

    Novogen took this over 8 years later – October 2013 Genscreen partners Trobio project with Australian ASX-listed Novogen Ltd – http://www.genscreen.com.au/october-2013-genscreen-partners-trobio-project-with-australian-asx-listed-novogen-ltd#more-256

    31st of August 2015 Gunning is presenting TR100 in Europe – TR obviously being the link to the TRobio project. question is why not “Anisina” since its the main drug candidate or speculatively might TR100 have a lot in common with Anisina.

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      • I don’t feel like I’m getting warmer – I already knew all that history along with the SBM’s and the links to the old Novogen & MEIP – but speculatively – Gunning appears to be distancing himself from Novogen (I can’t even find mention of them on Gunning’s UNSW page).
        I agree with Gunning being the nexus & I’m forming a view that he should never have accepted a board position at Novogen but may well have done so to keep an eye on his baby and who knows he may well wish to leave but Novogen have kept patenting around the atm’s to fence them in. If he was to leave then Stehn might also get the chop and they’ve potentially lost all that work paid for by kids charities. I found it interesting that after the former vet left that the old Novogen hand – Andrew Heaton got busy putting more patents applications around the atm’s but we’ve heard little of anything else going on.

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      • Questions:

        1) why post a confirmatory article about mechanism of action YEARS after? Have you followed the story on the “mechanism of action”, it’s evolved quite a bit.

        2) why present data on TR100 – an “early” ATM – indeed why even bother investing time and energy in a non-pipeline compound?

        3) why isn’t Novogen all over the Anisina program, including the charitable component?

        4) why, despite talking about it for months and months (years?) do we still not have any basic toxicology data?

        In the drug development space, when we are not sure whether a lead program will work or not, companies will often publish data on related drugs because if there are issues, the “actual” drug doesn’t get tarnished as much. I am willing to bet you that TR100 is not as potent but also not as toxic as “Anisina” (or something like that).

        In my opinion, Novogen has royally screwed itself by talking up the potential of Anisina on paediatric cancer but I am willing to bet that the company has a preliminary inkling that the drug is too toxic and is distancing itself from the clinical proof-of-concept. If the drug was good, the company would be all over it.

        Unfortunately, that’s what you get when you show a lack of integrity and talk up a program with ZERO evidence that you actually have a real drug candidate. Until Novogen has completed a full set of IND enabling studies, IT DOES NOT HAVE A PRODUCT CANDIDATE. The company hasn’t completed tox studies (could have been done 3 times over in the time I have been writing about Novogen) and keeps pushing back clinical timelines – I think it is because the company knows something and is gunshy.

        How else can you explain a huge balance sheet sitting there doing nothing? Even more telling is that the company is not funding an early clinical PoC! Doing a clinical study in cancer – even kids’ cancer – can be relatively fast and low-cost, especially in Australia. In some states, like WA, the state will even indemnify a pilot study.

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  6. Great research Hannibal.
    I’m aware that it takes time, effort and money for quality scientific research to occur, but one of Hannibal’s references infers that Genscreen’s ATM platform was not too far away from Phase II clinical trials – that was in 2005. For the sake of people with cancer, those who wish to help via financial donations and of course those wiling to invest in a genuine company with ethical principles, we need a more open and transparent system.
    Keep up the good work gentlemen.

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    • Steve I actually want something to be there in any of this TR range or even this “Anisina” as you could well imagine lots of people put their hands in their pockets for kids cancer research and many undertake volunteer fundraising as well. The Genscreen reference I posted:

      “The CEO of Genscreen, Ian Dixon, announced that Trobio was an exciting addition to the existing portfolio of Genscreen; and represented a significant opportunity for a drug development project to progress towards a Phase II trial and eventual partnership with an international partner.”
      http://www.genscreen.com.au/17th-september-2005

      The first reference to compounds was made by Genscreen in August 2009:
      http://www.genscreen.com.au/august-2009

      Also I found this from August 2013:

      “A Novel Class of Anticancer Compounds Targets the Actin Cytoskeleton in Tumor Cells”

      “Disclosure of Potential Conflicts of Interest”

      “J.R. Stehn has ownership interest (including patents) in Trobio Pty Ltd and is a consultant/advisory board member of Genscreen Pty Ltd. H. Treutlein is employed (other than primary affiliation; e.g., consulting) as a CEO in Computist Bio-Nanotech. I. Dixon is employed (other than primary affiliation; e.g., consulting) as director and shareholder, has commercial research grant, and has ownership interest (including patents) in Trobio Pty Ltd and Genscreen Pty Ltd. P.W. Gunning has commercial research support and ownership interest (including patents) in Trobio Pty Ltd. No potential conflicts of interest were disclosed by the other authors.”
      http://cancerres.aacrjournals.org/content/73/16/5169.full

      Trobio Pty Ltd is still registered – https://connectonline.asic.gov.au/RegistrySearch/faces/landing/SearchRegisters.jspx?_afrLoop=1612658990282956&_afrWindowMode=0&_adf.ctrl-state=16m6v9ay3r_4

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  7. Pingback: The Questionable Ethics of Anisina – Part II | The Long Tail

  8. After realising that it’s now been around 2 years since Novogen acquired the ATM “platform” from Genscreen, I’ve become concerned as to why it’s taken so long to achieve an outcome. I’ve reasoned that maybe Novogen have misplaced some important piece of information, so I’ve managed to locate a few important sites which might help them accelerate to a conclusion.
    This first site refers to an American stockbroker, who advises on page 7, underneath graphs indentified as exhibit 25, that the drug Anisina = TR100

    http://www.novogen.com/pdf/HCWainwrightReport.pdf

    Now the second site refers to a Chemical company called Sigma-Aldrich who can supply TR100 for $139.00 for 5mg, or for the more value conscious $559.00 per 25mg. As well, at no extra cost, the site offers the complete chemical structural formula for TR100. I do hope that Mr Heaten from the technical branch at Novogen, gets the opportunity to read this, before attempting synthesis.

    http://www.sigmaaldrich.com/catalog/product/sigma/sml1065?lang=en&region=AU

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    • Hmmm…. I took a look at the MSDS for TR100. It’s supposed to disclose if the material is manufactured by a 3rd party, but seems to suggest the material is indeed synthesised by Sigma.

      As usual, your sarcasm is priceless.

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    • Good research Steve – I can’t believe they mass produce this already and you can buy it- when I click on the “FROM” link it states its shipped from the United States and available on the 9/9/15 (yesterday)
      Read the MSDS and the powder is pretty toxic. If Sigma are producing it then it must be under licence to someone – It doesn’t look like its Novogen?. I’m shaking my head at this – the more I read the stranger it gets? TR100 might still be under this Trobio or Genscreen but if so then speculatively Novogen didn’t get all of the compounds? Seems very odd that you can purchase TR100 because even that release from Novogen about TR100 talks of the ATM’s as “Technology now owned by Novogen” Why would TR100 be produced in quantity if, (again referring back to the Novogen release dated 31/8/15), and I quote “Professor Gunning said the study used an early anti-tropomysin (ATM) compound, TR-100” further on – “TR-100 is a first generation ATM compound having been superseded by Novogen’s lead compound, Anisina.”

      http://www.novogen.com/news.html

      Obviously someone wants this TR100 produced and it looks like Sigma can produce quite a bit of it for whovever orders it? Again great find Steve though it just creates even more questions in my mind.

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      • Guys, please, understand the science and the difference developments of compounds in research compared with extending that to developing compounds for therapeutics. I’ve read the published literature. TR100 appears to be a very early generation candidate compound to demonstrate targeting a tropomyosin isoform. It was used as a research tool to demonstrate the principle that tropomyosin could be targeted by a molecule, for lab research in cell models, and to investigate the chemistry of its interaction with the target molecule and the consequences. It appears not intended as a therapeutic compound, but the general class is hoped to head that way. In drug development, there are multiple rounds of synthesis of new candidate molecules designed to make something that is therapeutically compatible, and this gets informed by the investigations into the biochemistry of the earlier generations (presumably like TR100) which can be fed into the computational models to inform the new generations. As something that can target tropomyosin, TR100 can be supplied by a company like Sigma as a research tool to investigate the biochemistry involved in disrupting this molecule and how it affects the cell – for basic research in cell biology and understanding cancer biology.

        Seriously, Sigma is a very widely used (by scientists) company specialised in research, not therapeutics, which sells thousands of compounds that can be used as useful tools in research labs for basic science. And this is what presentations or publications involving TR100 that I’ve seen are about (basic cell research, not therapeutics) – it’s pretty clear if you actually bother to read the science and have the slightest understanding what the Sigma market is. Anisina is a completely different kettle of fish, developed multiple generations of computational and biochemistry-heavy compound design after TR100 but in the same broad class, with an aim for therapeutic application and compatibility, hence it’s pharmaceutical track development.

        If there is still confusion as to the difference between basic research application supplies sold at Sigma compared with a drug pipeline at a pharma, here’s the authors own description from the journal publication quoted in an earlier post (A Novel Class of Anticancer Compounds…) about TR100 and its subsequent class : “This proof-of-principle study shows that it is possible to target specific actin filament populations fundamental to tumor cell viability based on their tropomyosin isoform composition. This improvement in specificity provides a pathway to the development of a novel class of anti-actin compounds for the potential treatment of a wide variety of cancers.” ie TR100 helped establish a pathway to develop therapeutics such as Anasina. It’s pretty clear. The structure is also published in this article, so there’s nothing new here.

        As a scientist, I’m not qualified to comment on the company or charity side of things, but I do understand how drug pipelines are first established by scientific principles and then later refined by new compounds in partnerships with pharma to move towards the clinic. And how scientists also use chemical compounds from places like Sigma for basic research questions not immediately related to the therapeutic goals of pharma pipeline drugs like Anisina, but may help shed light on the science around it. Please try not to mix stuff up -it doesn’t benefit anybody’s oversight.

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      • Hi Dave, thanks for the useful – albeit slightly high-handed – commentary.

        We all know what Sigma is. We all understand PoC, but I think you have missed the point. The point is that the company has basically made zero progress despite a lot of time and money. There isn’t a whole lot of science reported around Anisina because, well, there isn’t a whole lot of science. It’s basically mythology. Anything that is reported around anti-tropomyosin biology is always TR100. Your last paragraph, however, is completely academic. When you start asking people for money, particularly charities, to run clinical trials, you had better have a clear idea around what you are doing.

        Thanks for reading.

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  9. I think that Mr Gunning and Ms Stehn are absolutely genuine, are “real scientists” and have developed a molecule that needs to be tested in human clinical trials, as soon as possible. They have their reasons for choosing Novogen in order for this to happen and I’m sure that those reasons are only good. The question is, can they transform the Novogen “red clover” and “super benzopyran” culture into a serious cancer drug development company, that will produce compounds which will really help people suffering from cancer? I really hope so.

    All the best.

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    • Well if they are genuine, it’s time to get productive and stop screwing around. This is a company that spends more money each month being a public company that it does on pre-clinical development of Anisina.

      Just to be clear.

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    • Yes I think the same thing Steve. I hope for the kids it proves up something & as far as the red clover culture at Novogen I couldn’t agree more – not a great look for a kids cancer charity but then again seems no-one else was stepping up to the plate and it sure did give Novogen a better look – be ironic if it proves to be the real deal these atm’s

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  10. One thing is for sure and that is the announcements every 5 minutes have dried up since the former vet left so who knows maybe much of the “red clover” culture left with him. Scrutiny of these companies hopefully will drive more change – I’m sure they don’t enjoy being lampooned when they like to be seen as being dead serious.
    Keep up the good work Chris

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