Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘AR-V7 Biomarker’

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Miami Beach Lifeguard Tower

This week I’ve been at an American Association for Cancer Research (AACR) conference in Miami on “Targeting the Vulnerabilities of Cancer,” part of their Precision Medicine Series (Twitter #AACRpm16).

What’s interesting about AACR small specialist meetings is as well as listening to high quality talks, they create a relaxed atmosphere for networking and catching up with experts informally. The conference this week was relevant to anyone with an interest in cancer drug discovery.

Dr Bernie FoxAlthough cancer immunotherapy remains the hottest topic in cancer drug development, we shouldn’t forget that there are other therapeutic targets worth exploring; several potential new opportunities were highlighted in Miami.

As readers know we don’t share unpublished data on the blog, so what I’ve done is provide a top-line summary of some of the strategic themes and key take homes I took from several of the presentations.

As an aside, If you haven’t already done so, do listen to the latest episode of the Novel Targets podcast – Of Mice and Men – it features excerpts of interviews recorded at the recent AACR annual meeting in New Orleans. I was surprised by some of what I heard!

For more information on forthcoming AACR meetings and workshops, check out the events calendar on the AACR website.

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After the intensity of gastrointestinal cancer, we now turn our attention to genitourinary (GU) cancers with the upcoming ASCO GU meeting later this week in Orlando.

Two of the big topics here will be prostate and renal cell (RCC) cancers.

Unfortunately, the long awaited data in adjuvant RCC demonstrated that early treatment with sorafenib or sunitinib did not improve outcomes in locally advanced kidney cancer after resection. According to the ASCO press release, the trial conducted by Dr Haas and colleagues at U Penn discovered that:

“The average period to disease recurrence was similar between those who received sorafenib or sunitinib after surgery (5.6 years) and those treated with placebo (5.7 years).”

We will therefore turn our attention to castration resistant prostate cancer (CRPC).

One of the recent and ongoing controversies is splice variants, especially AR-V7, which is thought by some research groups to confer resistance to the hormonal therapies, enzalutamide and abiraterone. The big question though, is does it, and how useful is an assay in helping to determine appropriate therapy? Are there other factors at play?

We looked at the latest data and put the findings in context with what we know from other published research.

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At the 2014 ESMO Congress in Madrid, Mary-Ellen Taplin, MD (Dana-Farber Cancer Institute, Boston) presented the results of the Tokai Pharmaceuticals (NASDAQ $TKAI) ARMOR2 clinical trial of galeterone in men with advanced prostate cancer.

ESMO 2014 Dr Taplin Galeterone ARMOR2 Presentation

Galeterone has a novel triple mechanism of action. In effect, it is a CYP17 lyase inhibitor (like abiraterone) that has additional anti-prostate cancer actions including androgen receptor (AR) inhibition (like enzalutamide). It also causes AR degradation that decreases AR levels.

Tokai’s IPO last month is reported by Renaissance Capital to have raised $98M for the company, with most of the funds going to prior investors including Novartis Bioventures which owned 28 percent.

Shares in $TKAI were initially priced at $15. They soared to a high of $30 thanks to high insider buying and a high trading volume. Novartis Bioventures were reported by Renaissance to have bought $20M.

As of publishing this post, the stock is now trading at $15.40, slightly above it’s IPO price. So have Novartis and others made a good investment?

Tokai Pharmaceuticals Stock Info Oct 3, 2014The market cap of $TKAI, according to their Investor Relations page (screenshot pre-market Oct 3, 2014 shown above) is $336M – not high for a company about to enter phase III drug development.

Readers are no doubt aware of the Feuerstein-Ratain rule that predicts a phase III cancer trial will be a failure when undertaken by a company with a market cap less than $300M. As Adam noted in his May 6 story on The Street earlier this year, “For companies with market caps between $300 million and $1 billion, the oncology phase III success rate is 59%.

The big questions now are did the data for galeterone from the ARMOR2 trial impress at ESMO 2014 in Madrid and what are the challenges and opportunities in the planned phase III ARMOR3-SV trial? 

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DISCLAIMER: Please note this piece offers no stock advice, is not a solicitation to invest in $TKAI and makes no recommendation on whether to buy or sell. It merely offers commentary and analysis of the data presented at ESMO 2014. Readers should do their own due diligence prior to making any investment decision.

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We continue our “pre-game” coverage of the 2014 ESMO Cancer Congress in Madrid with a look at what’s hot (or not) in prostate cancer at ESMO.

The treatment of advanced prostate cancer has been revolutionized in the recent years with the approval of new treatment options such as abiraterone acetate (Zytiga), enzalutamide (Xtandi) and radium-223 dichloride (Xofigo).  We’ve also seen some expensive flops in late stage development such as: dasatinib (Sprycel), TAK-700 (Orteronel), custirsen (OGX-011), lenalidomide (Revlimid) and cabozantinib (Cometriq) – all failed to show a significant overall survival benefit in large phase III trials.  In addition, sipuleucel-T (Provenge) although an approved new treatment, is considered by many to be a commercial failure, which highlights that it’s not just about obtaining regulatory approval as a key success factor.

The results of the accrued phase III trial with ipilimumab (Yervoy) in the pre-chemotherapy setting (recall that the ipilimumab post-docetaxel phase III trial was a failure) is eagerly awaited.

Next up in the pipeline we have next-generation androgen receptor (AR) inhibitors such as ODM-201 (Bayer/Orion) and ARN-509 (JNJ/Aragon). Phase III trials with these new AR inhibitors are recruiting for the treatment of non-metastatic castration-resistant prostate cancer (CRPC).

Other novel compounds of note earlier in development include galeterone for which a phase III trial is planned, and bromodomain inhibitors.

So what’s hot at ESMO 2014 in prostate cancer?

In the second of our preview series we take a critical look at some of the oral presentations in the preliminary ESMO program: what’s a rehash of ASCO 2014, and what new data are worth looking out for when the abstracts are published?

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Yesterday saw the news that Tokai Pharmaceuticals ($TKAI) have filed plans for a $75M IPO, largely based on the potential of their phase 2 prostate cancer compound, galeterone.

My first reaction on seeing this was $75M – that’s a pretty small number.

It’s been many years since I project managed drug development trials but $75M does not go a long way if you want to run a global phase 3 program. It’s certainly pails into insignificance in comparison to the recent $308M raised by Juno in Series A & B financing.

A cynical view would be to see this as the initial investors looking for a ‘save face’ exit strategy. Tokai have spent the last 10 years seeking to bring a novel prostate cancer drug to market, and they are still only in phase 2. To put this in perspective, they were initially ahead of Medivation!

Fast forward 10 years and the prostate market is now highly competitive, with other new products ahead of galeterone in development including next generation androgen receptor antagonists: ARN-509 (acquired by JNJ from Aragon) and ODM-201 (Bayer/Orion). We’ve also seen a several drugs that showed promise in phase 2, fall by the way side in phase 3; dasatinib from BMS and Orteronel  (TAK-700) from Takeda/Millennium readily come to mind.  Caveat emptor!

At ASCO 2014, there was a lot of interesting data in the oral prostate cancer session, which provided insights into the challenges (in addition to the competition) and opportunities that may exist for galeterone.

I have no intention of taking any future position in $TKAI. This piece offers no recommendation on whether you should invest or not.

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A predictive biomarker for prostate cancer drug resistance may lead to new drug development opportunities.

At ASCO 2014, one of the prostate cancer highlights was the oral presentation by Emmanuel Antonarakis MB BCh, Assistant Professor of Oncology at Johns Hopkins.

He presented elegant research, albeit in a small group of patients, about how constitutively active splice variants (AR-V’s) may represent one potential mechanism of resistance to androgen receptor (AR) signalling inhibitors such as enzalutamide (Astellas/Medivation) and androgen synthesis inhibitors such as abiraterone (JNJ).

I spoke to Dr Charles Ryan, Professor of Medicine and Urology at the University of California San Francisco (UCSF) about the significance of the data to clinical practice, and the new drug development opportunities that may follow-on from it.

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