WntResearch will present "exiting" Phase I results November 6 in Boston

2015-10-13 21:17, Edited at: 2015-10-14 09:26

The WntResearch drug candidate Foxy-5 has emerged as a possible new blockbuster in a novel cancer treatment concept targeting the lethal metastatic process. Phase I results for biomarkers will be presented in a newsrelease, most likely no later than around November 6 since WntResearch will present that date at AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

WntResearch http://www.wntresearch.com is a Swedish drug development company. Its Foxy-5 project has been highly ranked and received grants from both the Swedish cancer fund and the EU related Eurostars program totalling around 7 million dollars or so up to date.

The Foxy-5-project involves the scientifically very promising drug candidate Foxy-5 which is a small molecule, a formylated hexapeptide that mimics the glycoprotein Wnt-5a by binding to the Frizzled-5 receptor on the surface of the cell.

Both Foxy-5 and Wnt-5a can stimulate action through direct receptor agonism which results in certain downstream effects after activating the Wnt-5a signalling pathway.

The expected action of Foxy-5 in a clinical context is to inhibit metastasis in some very common forms of cancer and thereby increase the quality of life and life expectancy of many patients.

Preclinical studies from 2014 and 2015 indicate that Wnt-5a also may have an anti cancerstemcell effect in breast and colon cancer and this may apply to Foxy-5 as well.

http://cancerres.aacrjournals.org/content/early/2015/03/12/0008-5472.CAN-14-2761.full.pdf+html%C2%A0

http://events.embo.org/14-signalling-cancer/Abstractbook_EMBO_Cavtat-2.pdf

See pdf page 166 taken together with :

http://www.gastrojournal.org/article/S0016-5085(15)01097-5/abstract

A Phase I dose escalating clinical study was completed in September 2015. It was not only investigating toxicity and pharmacokinetics but also pharmacodynamics i.e. several biomarkers for antimetastatic effect of Foxy-5 in 27 patients with breast, colon and prostate cancer.

https://clinicaltrials.gov/show/NCT02020291

The results will be presented in a newsrelease, most likely no later than around November 6 since WntResearch will present at AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston. The abstract will be published October 26 and therefore some news about that also may be released to the stock market.

The antimetastatic effect of Foxy-5 was for example investigated indirectly by studying the number of circulating tumor cells (CTCs) in the blood which represents a marker for disease prognosis in patients with breast, colon and prostate cancer according to several scientific studies.

Breast cancer:

http://clincancerres.aacrjournals.org/content/11/10/3678.full

Colon cancer :

http://www.ncbi.nlm.nih.gov/pubmed/20143276

Prostate cancer :

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743247/

Next a Phase Ib and thereafter a Phase II study will be performed after which, if not before, exit is expected to occur either by out-licensing Foxy-5 to a Big Pharma company or by selling the project or the whole company.

Proof of concept through biomarkers for the antimetastatic effect of Foxy-5 is a goal in Phase Ib which may be sufficient for exit. A Big Pharma partner could benefit from performing Phase II studies in breast and prostate cancer as complements to the planned Phase II colon cancer study.

Spectacular take overs since 2014 concerning promising cancer drug development companies in Phase I have occured, such as USD 725 million + 1 billion milestones paid by Roche for the breast cancer oriented Seragon.

This implies that a possible takeover bid on WntResearch should be very high, especially since Foxy-5 should have a broader market potential and, importantly, likely could be the first known drug to directly target the metastatic process and therefore represents a revolutionary, paradigm shifting, concept in treating breast, colon and prostate cancer, in combination with drugs that kill cancer cells.

Around 2 million new patients each year worldwide or half of all the 4 million patients diagnosed with these forms of cancer could benefit from Foxy-5, i.e. those with a low or no expression of Wnt-5a in their primary tumors.

The world market for breast, colon and prostate cancer drugs is estimated to be worth 27-46 billion dollars within 2-8 years according to different sources.

The 10 best selling cancer drugs each generate revenues of around 2-6 billion dollars a year.

If Foxy-5 reaches the market it should become the first approved drug that specifically targets the metastatic process by inhibiting cancer cells from migrate and invade and may reach the top 10. In theory Foxy-5 could become the number one selling cancer drug since metastasis is now responsible for around 90 % of the deaths in cancer.

A price of USD 2-4 billion dollars or more after Phase I seems to be a plausible sum if a Big Pharma company buys out all the shareholders of WntResearch or just the Foxy-5 project. The company value after a licensing deal could be similar.

The founder of WntResearch, professor Tommy Andersson, is also the brain behind Foxy-5 (and its relation to Wnt-5a) . He is CSO (Chief Scientific Officer) of WntResearch and one of the two biggest shareholders.

No single shareholder controls 10 % or more of the outstanding shares in WntResearch which is therefore a small but extremely attractive prey for a Big Pharma takeover bid which seems likely to occur within 1 year considering the very promising Foxy-5 project and a possible proof of concept.

The risk adjusted stock price target in the Swedish stock analysis http://www.loparn.com is calculated to SEK 1337, compared to the current (as of Oct 13) stock price for WNT.ST of just around SEK 62, which corresponds to a market capitalization of little over USD 120 million.

Thus there is an extremely attractive risk/reward ratio in this stock according to the analysis.

The preclinical work regarding Wnt-5a and Foxy-5 is considered to be of a very high quality according to my wife PhD Ann-Cathrin Engwall (born Svensson) and me. I consulted her in April 2013 to examine the Foxy-5 project in detail from a scientific point of view and she was very impressed. At least 36 different scientific articles concerning Wnt-5a and/or Foxy-5 now support the project in breast, colon and prostate cancer.

Now, why exactly is Foxy-5 likely to become succesful ?

The answer can partly be derived from the following scientifically based observations :

1. It has been shown that half of the patients with breast, colon and prostate cancer, i.e. those with a relatively high expression of Wnt-5a in their primary tumors, have a significantly better prognosis of their disease with a lower risk for developing metastases and therefore also with a longer diseasefree life. Scientific data supporting this can be found in the following articles :

Breast cancer:

http://cancerres.aacrjournals.org/content/62/2/409.long

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0070890

Colon cancer:

http://cancerres.aacrjournals.org/content/65/20/9142.full

Prostate cancer:

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026539

http://www.ncbi.nlm.gov/pmc/articles/PMC3544436/

2. Foxy-5 has been formylated and therefore the risk for the human body to break it down before ithe molecules reach their target, the Frizzled-5 receptor, is minimized.

http://www.jbc.org/content/281/5/2740.full.

3. Foxy-5 reduces metastasis by 60-90 % in a mouse breast cancer model in vivo where the expression of Wnt-5a is low. It is also shown in vitro, for both Foxy-5 and Wnt5-a, that they inhibit cancer cells to migrate and to invade (such as other organs).

http://clincancerres.aacrjournals.org/content/14/20/6556.long

Foxy-5 and Wnt-5a reduce metastasis in mouse prostate cancer models in vivo.

http://tinyurl.com/mx4s4g4

http://www.bone-abstracts.org/ba/0003/ba0003OC5.4.htm

So does Wnt-5a in colon cancer.

http://onlinelibrary.wiley.com/doi/10.1002/jcp.24566/abstract

4. Foxy-5 mimics the glycoprotein Wnt-5a, by binding to the Frizzled-5 receptor on the surface a cell. Both Foxy-5 and Wnt-5a can stimulate action through direct receptor agonism which results in activation of the Wnt-5a signalling pathway. Wnt-5a is highly conserved between species, including man and mouse (98 %) indicating that its function is fundamental. Research shows several downstream antimetastatic effects in breast cancer. The Frizzled receptors are also highly conserved between species. Therefore the probability for success in clinical trials is elevated.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0058329

http://jcs.biologists.org/content/114/11/2043.long

http://www.jbc.org/content/284/16/10968.full.pdf+html

http://onlinelibrary.wiley.com/doi/10.1002/ijc.10752/pdf

http://www.jbc.org/content/284/40/27533

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592795/

http://www.sciencedirect.com/science/article/pii/S1574789113000665

5. Metastasis is now responsible for around 90 % of the deaths in cancer.

http://blogs.cancer.org/expertvoices/2013/01/23/unlocking-the-mysteries-of-metastasis/?_ga=1.230734943.1975696295.1443898260

6. In the now completed Phase I clinical study so far no side effects of Foxy-5 have been reported to the market.

7. "Exiting", according to CEO Nils Brünner, clinical results will be presented in Boston Nov 6. The presentation poster abstract which will be released online Oct 26 is titled :

"Targeting the Wnt-5a signalling pathway as a novel anti-metastatic therapy"

CEO has several times stated that he is very optimistic about the Foxy5-project and has talked about a "paradigm shift" in cancer treatment, and he should know since the Phase I study was an open label trial and most of the biomarker data collected should have been known for several months now. He is also, obviously very optimistic, aiming for a Foxy-5 market approval after Phase II.

Thus the important mechanism of action of Foxy-5 as a metastasis inhibitor is now well understood, which reduces the risk for the clinical studies to fail, all being equal.

Of all the patients with breast, colon and prostate cancers around 50 % with low or no expression of Wnt-5a could be expected to be helped by receiving Foxy-5 as a drug to reduce the risk for developing metastases and increase their diseasefree life expectancy.

An official presentation of the Foxy-5 project :

http://www.wntresearch.com/media/9372/sedermeredagen-2015-lund-260315.pdf