oncology | Pharma Strategy Blog

ASCO 2010 Preview #2: PI3K and mTOR inhibitors

By MaverickNY on May 12, 2010

One of the interesting things about scientific conferences such as AACR and ASCO is that everyone looks at the same data differently as if it were through a kaleidoscope.

Brand marketers focus on their competition by tumour type or disease, scientists look at specific mechanisms or pathways, investors look at particular companies and so on.

Someone asked me the other day how I analyse the data. I hadn't really thought about it much until then, but on reflection what I'm interested in is trends and how research evolves from a big picture science view so that means I look at pathways like a true biochemist. This also teaches us where the gaps are and what opportunities may arise in the future. It's not exactly rocket science, but it is a useful approach sometimes.

Image via Wikipedia

One of the clear trends emerging at AACR the other week is that dual inhibition of both the PI3K-mTOR and RAS-ERK pathways may be necessary in some cancers such as melanoma to reduce cross-talk, feedback and feedforward loops, drug resistance and loss of PTEN gain of function, just as one might also target IGF-1R and EGFR to reduce cross-talk and add in another inhibitor, eg MEK or AKT.

Given the increasingly critical role of MEK and AKT in various combinations in the future to reduce the potential for drug resistance occurring, this bodes well for a host of companies. I wasn't, therefore, surprised to see Novartis snap up Array's MEK inhibitor (ARRY-162) given they already have an mTOR on the market (everolimus, Afinitor), two PI3-kinases in development and others including a RAS inhibitor. Having a MEK inhibitor as well may therefore give them a lot of flexibility with different combinations in multiple cancer types if this approach pans out.

Merck are also following a similar approach with their mTOR inhibitor, ridaforolimus, which they have finally grabbed commercial control of from their partner, Ariad. Let's not forget they also have an AKT inhibitor, dalotuzumab and a MEKi through their partnership with AstraZeneca to play with too.

This is all good news for several biotech companies though, if some big Pharma companies start catching onto the trend and realise they need may a PI3K-mTOR inhibitor and a MEK or AKT inhibitor to stock up in their pipeline before the field gets too crowded.

Which companies might have new and interesting data in this area?

Well, Keryx and Aeterna Zentaris, Semafore, Calistoga, Intellikine and a few others all have PI3K inhibitors in development, while Exelixis have a deal in place with sanofi-aventis for XL147 and XL765 and Roche/Genentech have a pan-PI3K inhibitor, GDC-0941. Novartis have two (BEZ235 and BKM120). Some of these compounds are single PI3K inhibitors and some are dual inhibitors of PI3K-mTOR.

Looking at the ASCO abstract titles, Exelixis appear to have the most abstracts in this area this year, so it will be interesting to see what sort of data they have across a range of different tumour models and early phase I results in solid and hematologic malignancies, with a variety of different combinations.

One session I'm really looking forward to at this year's ASCO is a Clinical Science Symposium entitled, "Paths for Clinical Development of PI3K Inhibition" with some of the heavyweights in the field such as Neil Rosen (MSKCC), Skip Burris (Sarah Cannon), Jose Baselga (Spain) and Carlos Arteaga (Vanderbilt). Arteaga is presenting a talk in that session entitled, "Next steps in clinical development of PI3K inhibitors?"

More later on this blog after the posters and the data become available at the meeting.

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New Product Marketing

By MaverickNY on April 27, 2010

One of the things about oncology or any other therapeutic are new product development and marketing is that you get to spend a LOT of time at scientific congresses like AACR in DC the other week, which means early to rise and late to sleep:

Source: Personal iPhone – view of over the Potamac and Georgetown, DC from Arlington, VA.

Anyone who thinks these meetings are junkets or jollies should join me on my schedule next trip;sometimes there isn't time to eat or by the time you do have a free slot it's too late. Often, it means 18 hour days and a day back in the office is a relative rest. There's always thought leaders to talk to, sessions to attend, media briefings, poster sessions (you can walk miles at those alone), plenaries etc, not to mention clients as well. Fitting it all in makes for jam packed days.

The interesting thing about new data though, is that while trends may be obvious to those following the specific disease area, they are not to others. I always find it amusing watching the teams of young things running around with their crib sheets frantically collecting poster handouts, rudely barging past people and trying to discreetly snap the posters without security catching them.

In DC, I asked one what they did with all the data they amassed. It turns out they just dump it all in a report for their client by whatever category seems apt. No strategic analysis, what it all means or even trend spotting, just a data dump. Ugh.

Sometimes less really is more.

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Are you a crazy deranged fool (CDF)?

By MaverickNY on April 7, 2010

The other week someone asked me why I do so much work specialising in oncology and cancer, which admittedly can sometimes bring more sad news than good.

I answered simply: "because I'm a crazy deranged fool!"

Source: Hugh

I follow Hugh MacLeod's cartoons daily and also subscribe to his excellent newsletter. On bad days he keeps me sane, on good days I laugh out loud.

What on earth is a 'crazy deranged fool' you may be wondering?

According to Hugh:

"A CDF is my term for somebody like me, i.e. somebody who actually has the temerity to TRY to do what he loves for a living, as opposed to shlepping for his daily crust."

Running a consulting business and going to many scientific and cancer meetings has it's benefits – one of them is realising you're getting paid for doing something you love and have a lot of enthusiasm for.

Making sense of data is fun; finding patterns and trends amongst a mass of information on a huge variety of different cancers is sometimes like unravelling DNA.

Are you a crazy deranged fool?

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Bioclinica biomarker symposium in oncology and neurology #bioc

By MaverickNY on March 29, 2010

Tomorrow, I will be in Princeton, NJ for a one day meeting focused on addressing the Current and Innovative Imaging Biomarkers in Neurology and Oncology Drug Development, hosted by Bioclinica.

If you have any questions about the event, please send a tweet to @maverickNY and I will do my best to answer them on Twitter. Comments on this widget will not be monitored until the end of the day as wifi and internet access is likely to be limited and I'll be tweeting from my iPhone.

If interested, you can follow the synopsis from the live tweets below by clicking on the Play triangle:

The event will involve some interesting speakers including the following:

Cornelis van Kuijk, MD, PhD

– Professor and Chair Department of Radiology, VU University Medical Center

Frederik Barkhof, MD, PhD

– Professor in Neuroradiology
Radiology and Image Analysis Centre, VU University Medical Center

Adriaan A. Lammertsma, MD, PhD

– Professor of medical physics and positron emission tomography (PET)
Nuclear Medicine & PET Research, VU University Medical Center

Ali Guermazi, MD

– Professor of Radiology
Director of Quantitative Imaging Center
Boston University School of Medicine
Section Chief, Musculoskeletal Imaging, Boston Medical Center

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An overview of Roche's oncology pipeline

By MaverickNY on March 26, 2010

At last weeks investor meeting held by Roche in downtown Wall Street, the Board reviewed the pipeline opportunities in a number of areas. Earlier this week I wrote about the non-oncology pipeline and today will form an overview of the cancer drugs in development.

One of the things that Roche is renowned for is life cycle management. They do this better than many in the industry in my opinion and it makes an enormous difference not only to continuity, but also long term revenues and performance. Too many companies take a short term view and do not think ahead to the future. This is a big mistake. Perhaps they get bogged down in classic silos or management do not see it as a priority, but it does make a difference.

Why?

Well, for starters, think about the basics of marketing. It is much easier to sell new products to existing customers than it is to sell existing products to new customers and even harder to sell new products to completely new customers.

Thus life cycle management is a smart strategy and done well, enhances the experience for everyone involved whether employees or investors. I only wish more companies paid closer attention to this important aspect of Pharma marketing.

The other thing I like about Roche's approach to R&D is rigorous and strong proof of concept studies (usually in phase II). Between Roche and Genentech, they both do this particularly well in oncology, it seems to be their signature. This partly explains why they mostly end up with a continuous wall of data across several products including trastuzumab (Herceptin), rituximab (Rituxan) and bevacizumab (Avastin). Of course, negative trials do occur but overall, they seem to have more positive trials than not. This partly explains why they have fewer phase III flops than say, Pfizer, because they spend the time in phase II working things out rather than rushing aggressively ahead on the basis of early evidence.

So what did we learn from the pipeline presentations last week?

There are late stage oncology products in development that look promising.

One example is trastuzumab-DM1, which is basically modified Herceptin with a potent cell killing agent, DM1, bolted on. The goal is to improve the action of Herceptin in metastatic breast cancer, and at the same time invetigate whether the xenograft data in a variety of cancers (breast, ovarian, lymphoma and prostate) with an armed antibody is an effective strategy in people. Recent phase II data from the San Antonio Breast Cancer Symposium in heavily treated women with metastatic breast cancer look encouraging. Phase III trials have already begun and if all goes well, filing is currently anticipated by 2012.

Also potentially strengthening the breast cancer franchise is pertuzumab, a monoclonal antibody that targets HER2. Early phase I trials in several cancer types produced so-so results, but more recent phase II data in breast (combined with Herceptin) and ovarian cancer (in combination with gemcitabine) published this month in JCO look interesting.

Perhaps the most exciting compound though, is PLX4032/RG7204, a BRAF inhibitor being evaluated in malignant melanoma. Currently available data suggests survival is improved by 6 months so the big question is what causes resistance to develop and how this can be overcome. Data on this compound is expected at ASCO, where many are keen to see how it stacks up with ipilimumab (BMS).

In hematologic malignancies, GA101 or galiximab is being evaluated in non-Hodgkin's Lymphoma (NHL) and chronic lymphocytic leukemia (CLL). It appears to target a different part of the CD20 isotope than rituximab and this may increase it's efficacy. Phase III trials began in 4Q09 thus it will be a little while before we see some results. There is clearly an unmet medical need in the 3rd line refractory disease for more tolerable agents and rituximab is very much the bedrock of treatment for both across multiple lines of therapy either alone or in combination with chemotherapy. A similar agent will likely have good take up with the right approach.

Genentech are investigating various new and improved approaches to angiogenesis, but these are in much earlier development and the bar is very high with bevacizumab (Avastin), even for the company who manufacture it. The list of anti-angiogenesis compounds that didn't make it to market is very long indeed.

I've left the best to last, as hedgehog (Hh) signalling is one of my favourite pathways – it always reminds me of the cheerful cartoon character, Sonic the Hedgehog. RG3616, licensed from Curis, is currently in phase II trials for advanced basal cell carcinoma and trials are also underway for medulloblastoma. If interested, you can find out more about the pathway and the science here.

Overall, the oncology pipeline has a nice mix of follow on compounds to strengthen life cycle management with a raft of monoclonal antibodies with different targets in new cancer types. Such a strategy should reduce risk and drive the future bottom line if the promise delivers in phase III trials.

Baselga, J., Gelmon, K., Verma, S., Wardley, A., Conte, P., Miles, D., Bianchi, G., Cortes, J., McNally, V., Ross, G., Fumoleau, P., & Gianni, L. (2010). Phase II Trial of Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer That Progressed During Prior Trastuzumab Therapy Journal of Clinical Oncology, 28 (7), 1138-1144 DOI: 10.1200/JCO.2009.24.2024

Makhija, S., Amler, L., Glenn, D., Ueland, F., Gold, M., Dizon, D., Paton, V., Lin, C., Januario, T., Ng, K., Strauss, A., Kelsey, S., Sliwkowski, M., & Matulonis, U. (2009). Clinical Activity of Gemcitabine Plus Pertuzumab in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer Journal of Clinical Oncology, 28 (7), 1215-1223 DOI: 10.1200/JCO.2009.22.3354

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Thoughts on the Roche non-oncology pipeline

By MaverickNY on March 24, 2010

Last Thursday, I attended the Roche Investor meeting in Wall Street, live-tweeted it using the hashtag #RocheIR and enjoyed an interesting event packed full with lots of information to digest.

Luckily, I bumped into an old colleague from Sandoz UK days and was delighted to learn that he is now Global Head of Regulatory at Roche. Of course, if you spend a day out of the office, you pay for it severely the next day with an even bigger pile of emails, client requests, RFPs and telecons to catch up on >.<

In fact, I was so busy, I didn't have time to post a blog about Thursdays event on Friday, but I did manage to interview Dr. Laura Esserman, the breast cancer surgeon at UCSF behind the fascinating I-SPY2 project that we discussed last week. More on that tomorrow.

The next two days of blogs will cover two reports on the Roche pipeline (non-oncology and oncology) and Dr. Esserman's unique perspective on getting the I-SPY2 project up and running, she has certainly made a difference shaking things up and challenging people's approach to drug development in a short space of time.

Let's begin with the non-oncology agents in Roche's pipeline.

Granted I normally write more about oncology, hematology and immunology here, but my background in Pharma started in more humble beginnings as a sales rep in the statin market, where we were also looking to differentiate ourselves by being an attractive option for people with diabetes, who have a much higher risk from long term CV mortality.

I was therefore very interested to see where Roche were going with this approach fifteen years later because we never had much success with it, despite Marketing thinking it looked to be an attractive opportunity no one was exploring. However, the undoubted long risk of earlier mortality and morbidity is subsumed to more urgent and immediate needs such as getting sugar levels under control and insulin levels regulated. Adding yet another drug into the mix complicates things for physicians considerably. Plus taking oral drugs over time also results in long term compliance issues, which may impact outcomes negatively.

Dalcetrapib is being developed for dyslipidemia and cardiovascular high risk patients. The first trial looks at artherosclerotic disease progression, lipid profile and biomarker profile and long-term safety profile of dalcetrapib in people with established coronary artery disease compared to placebo.

The primary endpoints include:

Nominal change from baseline to study end in coronary percent atheroma volume (PAV) of the target coronary artery assessed by IVUS.
Rate of change from baseline to study end in carotid intima-media thickness (CIMT) using B-mode ultrasound

The second trial is looking at the potential of dalcetrapib to reduce cardiovascular morbidity and mortality in stable coronary heart disease patients with recent Acute Coronary Syndrome (ACS) and evaluate the long term safety profile of the drug, again, compared to placebo.

The primary endpoint is defined as:

Time to first occurrence of any component of the composite cardiovascular event (cardiovascular mortality and morbidity)

These two phase III trials are currently recruiting people with coronary artery disease, so we won't know the results for quite a while, probably over the next 2-3 years. Such large scale trials are very expensive and time consuming to conduct. For all the the noise about statins reducing cholesterol, I sometimes wonder what impact they actually have on long term mortality and morbidity. Do they lead to any meaningful clinical change in outcomes, ie improved survival, rather than just lowering cholesterol per se?

Roche also have two drugs in development for type II diabetes, both of which are tongue twisters: taspoglutide, a new GLP-1 drug for Type 2 diabetes, and aleglitazar, for cardiovascular high risk in diabetes. The diabetes market is suddenly getting very crowded with numerous insulin, syringes, pens, pumps, and oral therapies all available.

Thus as a marketer, I'm wondering how new products into these segments differentiate themselves from existing therapies in this competitive disease? It's one thing to claim blockbuster potential, but quite another to capture the heart and minds of the physicians prescribing yet another me-too in a crowded existing market segment.

The $64M blockbuster question in diabetes for BMS's Onglyza, in the DPP-4 segment, rapidly turned into a spectacular $4M flop in the launch year. The inhaled insulins such as those from Pfizer and Mannkind were either withdrawn or struggle to make it to market. Two precautionary tales of humility in the diabetes market if there ever were some.

How Roche develop and differentiate taspoglutide and aleglitazar from existing segment leaders will therefore be an interesting process to watch. For now, we can sit back and wait for the various clinical trials to complete and see how the agents stack up. The phase III trials were initiated for aleglitazar were initiated in 1Q10, taspoglutide initial phase III results were released in 4Q09 and further results are expected in 2010. The results for dalcetrapib will not be available for a few years given the enrollment is just starting.

Two other non-oncology drugs in development include RG1678, a GLY-T1 inhibitor, for treatment of the negative symptoms of schizophrenia. The initial phase II results were positive last year and phase III trials are planned for 2010.

Ocrelizumab is a humanised CD20 monoclonal antibody similar to rituximab. The phase III trials were negative in rheumatoid arthritis and lupus, despite the agent being developed to reduce the development of drug neutralizing antibodies and infusion reactions. Recent studies, however, established that the safety risk associated with ocrelizumab outweighed the benefits and Roche disclosed that several patients died from infections so the development in RA and lupus was promptly suspended. Meanwhile, ocrelizumab is also being developed for the treatment of people with multiple sclerosis and a Go/No Go decision for the phase III development is expected this year.

Given the focus on five main disease areas including oncology, virology, immunology, metabolism and CNS, it is good to see new agents being developed in the metabolism and CNS areas after the long term focus on oncology with Genentech lately. How well they will do in the long run compared to the oncology pipeline, only time will tell.

Abbott makes some waves in Pharma

By MaverickNY on March 10, 2010

While listening to last week's presentation by BMS on their pipeline, one slide in particular caught my attention:

Source: BMS

Now, it wasn't the fact that BMS were second in their table of Total Shareholder Return (TSR) that was interesting to me, but that Abbott were first, and by a long way, according to the chart above. Of course, shareholder return is only one measure of performance and says nothing at all about putting customers and patients first, but that is another story/blog.

Recently, Abbott has been in the news with the acquisition of Solvay, a generics company, which added $3B to their revenues and last night it was announced that the company are also acquiring Facet Biotech, which was being pursued by Biogen Idec. The Biogen deal clearly fell apart after the company declined to raise their offer beyond $17.50/share. Abbott offered $27/share and thus a white knight was found. Interestingly, the Facet CEO, Faheem Hasnain, is a former employee of Biogen Idec.

The acquisition is a hot one, so to speak, and many of us in the industry have been speculating in vain on who the partner might be, so you would think that going on CNBC's Pharma's Market with Mike Huckman would be a nice coup for a small company. I thought it was odd though, to see that they seem a little publicity shy, as this tweet shows the company's rather gauche immaturity:

What do Abbott get from acquiring Facet?

Well, first we need to think about where Abbott is coming from. Most companies with either build on existing platforms and franchises or add new products in areas where they want to expand. Abbott is probably best known for it's immunology franchise, with adalimumab (Humira), its TNF inhibitor for rheumatoid arthritis and psoriasis.

Several companies, including Abbott and BMS, have embarked on a race to develop the next generation of Hepatitic C drugs and vaccines. Infectious diseases are not something that are going away fast, so this is seen as an attractive market segment by many.

Looking at the Facet acquisition, the pipeline is thus interesting because they have also been developing monoclonal antibodies but in different diseases including immunology and cancer. The lead compound is daclizumab, which is in phase II development for multiple sclerosis in partnership with… Biogen Idec. Facet own the exclusive rights to the asthma indication though.

There are also several anticancer antibodies such as volocizumab (solid tumours) and elotuzumab (multiple myeloma) in Facet's R&D. Oncology is an area where Abbott has been relatively weak, although they have some interesting compounds in development for liquid and solid malignancies. In 2009, a joint venture with TAP was concluded, adding Lupron, one of the best selling drugs for hormone-sensitive prostate cancer to the portfolio of currently marketed products.

Abbott may well see topline growth from it's cancer franchise in the future… if the pipeline products from their own labs or Facet's deliver. If those from Facet fail, Biogen Idec will be breathing a sigh of relief that their offer was turned down.

Such is life on the Pharma roller coaster.

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Why do some Pharma companies do well in oncology and other's don't?

By MaverickNY on March 3, 2010

A chance email yesterday from Matthew Herper of Forbes Health got me thinking. He was interested in whether a company, who have been successful in other therapeutic areas, could do well in cancer.

A question like that can quietly sit in the back of your mind for days percolating and brewing until you sit down and really think about it.

I've had some great opportunities to work in several different therapy areas including cardiovascular, dermatology, immunology, CNS, hematology and oncology. The last two have much in common, the others less so. But what makes them different, what factors are important to take into consideration and how do make it work?

Two of the big differences are data and science.

Cancer is much more technically complex than many diseases and the understanding of how the biochemistry and the drug interact can make or break a product. One of the first oncologists I ever met, a dour academic chap who did a lot of leukemia transplants and research in equal measure, memorably advised me in a most stern manner to "forget the fluff and puff, just show me the data!"

Cardiologists and dermatologists always seemed to ask 'how' questions… how much does this cost, how soon will you have slides for a lecture series, how many papers do you have published so far etc.

Oncologists are a different breed. They ask a lot of why and where questions… why should I use this drug, where is the evidence to show X or Y etc.

For me, it's about learning a completely different mindset and adjusting to a new customer focus. If your drug isn't better than what an oncologist has already, especially in efficacy, no amount of hype is going to give you a hook or an advantage. Risk-benefit trade-offs in a serious disease that may lead to deaths forces people to think about the treatments in another light.

Think about it, the most common questions an oncologist is going to hear from people who visit are:

Will I be cured?
Will it make me live a little longer?
Will the treatment make me feel better?

Intuitively, people with cancer focus on the most important things and for doctors hearing that many times during the course of a week, they will subconsciously be thinking that way too.

Going back to Matt's broad question, I was thinking about all these things yesterday while interviewing an oncologist about how he treats a certain cancer, which in rare cases is curative but in most situations 2) and 3) more clearly applied. My focus was a little sharper than usual because I found myself automatically asking why questions about a range of different regimens.

Now, some of the companies for the treatments he mentioned have indulged in typical marketing hype, with fancy programs, e-details and branded campaigns that could well have applied to an anti-hypertensive or skin cream. As the doctor walked through his treatment algorithm, I could almost imagine the critical survival charts on the wall in from of my desk. Finally, it became clear that he ranked them by the survival curves, with one exception that was reserved for a small, rare subset that had aggressive disease because the consequences of managing the concomittant myelosuppression were too high.

And there in is the rub.

Success in the oncology arena boils down to data and how well you stack up against the competition. Being first to market gives you a huge advantage too, since a hurdle is set and the ones afterwards are forced to demonstrate why they are better.

This is way many good marketers I've met avoid or dislike oncology: it's data driven, not marketing driven.

In oncology new products, the best thing you can do is focus on the data and find areas or niches where you can do well. It requires a more analytical approach to understand the science, work with the clinical and research teams and patiently build a blockbuster niche by niche. If a drug fails in an indication, either find another one quick or ditch it. Spend money wisely on more smaller phase I and II studies experimenting with different tumour types to match the biology of the disease with the drug's target. This is critical, but it also takes money and time with a high risk attached to it because more drugs fail than succeed.

Of course, once you get a drug to market, that's not the end. You have to practice 'kaizen' and continually invest more dollars in new indications. If you're too slow doing this, the second to market drug can be equivalent but have the advantage of a broader clinical program while you sat on your laurels for several years. Life cycle management means planning ahead for the second and third indications before you finish the first cancer type. If the first one fails, this also means you have a backup in advanced stages and that's a smarter strategy than everyone trying to get senior management's attention for resources and dollars if you put all your eggs in one basket.

Not every company has the scientific mindset and willingness to invest research dollars to succeed in cancer. Management by consensus doesn't work very well either, that just drags things down to the lowest (and often slowest) common denominator. You need passionate driven product champions who fight to the end and generate resources, focus and high priorities to get things moving by corralling the collective energy to get things moving at pace faster than the proverbial snail.

With regards to cancer pipelines, Roche/Genentech and Novartis probably have two of the most promising at the moment and are significantly ahead of the pack in my view. They invest heavily in science and research, as well as broad clinical programs that creates a continuous buzz. The mindset is clearly to accept a few negatives that are easily over shadowed by the many successes. This creates a groundswell and positive energy. Pfizer, Merck and BMS all have interesting pipelines, but also have to fight the internal entropy for execution as well.

Data matters. Execution matters.

Forget the hype in oncology and think about making a real difference to the lives of people with cancer and intelligent ideas around the concept of artisanal marketing, which my buddy Morgan Brown described in an intelligent and thought provoking post this week:

"Thoughtful, insightful, honest, embracing complexity and celebrating the craft of the product or products themselves."

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San Francisco: A hotbed of oncology Biotechnology

By MaverickNY on February 15, 2010

We spend a lot of time researching biotechs in the oncology space and thus it occurred to me that many of them are located around the San Francisco bay area as a hub, in a landscape dominated by Genentech, now part of the Roche empire. San Francisco has good logistic connections, a lot of roomy office space, active research in several universities and provides a pleasant haven for science, academia, research and industry to all flourish.

There are far to many to mention in one blog post, but here is a quick update on some of the companies we’ve been following over the last couple of years in the cancer market (in no particular order):

Sunesis ($SNSS): Got off to a rocky start with the early development of voreloxin, but have refocused the clinical trial designs with some interesting phase I and II results to date in AML. The compound, a quinolone derivative that acts as DNA damaging agent, is also being developed in platinum resistant ovarian cancer. I’d like to see some comparative data in AML at some point, or at least a study with just a standard chemo in it compared to the standard + voreloxin, otherwise it will be hard to see exactly what the agent actually adds.

Poniard ($PARD): Poniard are developing a new generation platinum agent, picoplatin, that seeks to offer equivalent efficacy as existing platinums, but with less neuropathy that is common to existing treatments such as oxaliplatin.

Picoplatin got off to a good start with trials starting in small-call lung cancer (SCLC) and colorectal cancer (CRC). Early results looked promising. However, results from the pivotal Phase 3 SPEAR (Study of Picoplatin Efficacy After Relapse) trial of in the second-line treatment of SCLC did not meet its primary endpoint of overall survival. The analysis, based on 320 evaluable events (patient deaths), showed a hazard ratio of 0.82 with a p value of 0.089. The company felt that the main reason for the discrepancy lay in pateints in the placebo arm receiving more chemotherapy than the picoplatin arm after relapse occurred.

A randomised, controlled Phase 2 trial of picoplatin in metastatic CRC patients is ongoing. The study recently met its primary objective. Picoplatin, in combination with 5-fluorouracil and leucovorin (FOLPI regimen), was associated with a statistically significant reduction in neurotoxicity (p <0.004) compared to oxaliplatin given in combination with 5-fluorouracil and leucovorin (FOLFOX regimen). The results also suggested that FOLPI had similar efficacy to FOLFOX. More data is expected at ASCO in June.

Nodality: Is an interesting technology company that is developing next generation diagnostics by characterising cell signalling pathways. The concept is based upon proprietary flow cytometry technology, originally developed in the laboratory of Professor Garry Nolan and licensed from Stanford University.

Flow cytometry has been widely used to characterise cell surface markers on hematologic cells. Nodality are now utilising advanced quantitative flow cytometry to define the signalling networks within individual cancer cells, in order to enable biologically-driven clinical decision making for cancer treatment. Essentially, this technology can be used to determine changes before and after cancer treatment, eventually leading to the identification of appropriate biomarkers for treatments.

BiPar Sciences: Are developing BSI-201, a PARP inhibitor for the treatment of triple negative breast cancer and ovarian cancer. They signed a deal with sanofi-aventis last year and are now a wholly owned subsidiary. It looks to be a promising agent, albeit with a short patent life. The race to market against KuDos/AstraZeneca will be an interesting one to watch over the next couple of years. How will the two PARP inhibitors stack up? Time will tell. They also have a follow on PARP inhibitor (BSI-401) in development, and an anti-tubulin compound.

Exelixis ($EXEL): Have been in the news frequently over the last few years as they license out their in-house compounds to companies such as BMS, GSK, sanofi-aventis and Genentech. Their stated goal is to develop first in class or best in class compounds through their own discovery and clinical programs. The pipeline runs an interesting gamut of targeted agents to various pathways, including MET, VEGF, PI3-kinase, IGF-1R, MEK, RAF and others.

The most advanced agent (XL184) is in phase III development for metastatic medullary thyroid cancer (MTC) with BMS (aka BMS-907351). This is a very slow growing cancer, so a rapid development is unlikely. The compound is a multi-kinase inhibitor of VEGFR, MET and RET. It is also being tested in phase I/II trials for recurrent glioblastoma (GBM), non-small cell lung cancer (NSCLC) in combination with erlotinib and a phase I trial in advanced malignancies is also ongoing.

BMS probably have the biggest investment in Exelixis, having licensed at least 5 of their compounds in cancer. Time will tell if this proves to be a smart decision or not.

Plexxikon: Are a private Berkeley based company who focus on the discovery and development of small molecules in several therapeutic areas including cardio-renal disease, CNS, inflammation, metabolic disease and oncology. They are most known for their BRAF inhibitor, PLX4032, which is being developed for the treatment of malignant melanoma. BRAF is thought to be mutated in approximately half of melanomas and may be one of the drivers of the disease.

Plexxikon signed a deal to develop the agent with Genentech, now Roche, and phase III trials in melanoma were announced last month. This is definitely a promising agent to watch out for.

Facet Biotech ($FACT): have been in the news recently after Biogen Idec tried to purchase the company, but offers have been repeatedly rebuffed and dismissed as inadequate. The company was launched as a spin-off from PDL BioPharma, Inc in December 2008.

Facet are developing several compounds in the multiple sclerosis and cancer markets, including volociximab (solid tumours) and elotuzumab (myeloma). The MS agent in phase II, daclizumab, has received most attention but the oncologic agents are too immature to determine how effective they might be yet. Definitely one to watch out for though, if a white knight in the form of a big pharma with cash descends in the near future. The most obvious companies with cash and a declared growth by acquisition strategy are BMS and Celgene, but I’m not sure Facet would be a good fit for either. On paper, Biogen Idec was probably a better option.

There are plenty of other interesting cancer companies in the Bay Area, but these are a few that I’ve been watching. More will be covered in the next update of the cancer market in the area. New data will no doubt be presented at the forthcoming American Society of Clinical Oncology (ASCO) meeting in June.

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Why did Roche's Avastin lose steam in 4th quarter 2009?

By MaverickNY on February 5, 2010

This snippet from Reuters posted earlier this week while I was listening to the Roche earnings call in Basle, which was a nicely put together presentation:

"Roche Holding AG overhauled the sales efforts for its best-selling drug, the Avastin cancer treatment, after the company “lost steam” during the fourth quarter.

Sales of the medicine were hurt by a focus on selling it as a treatment for breast tumors, Pascal Soriot, the head of the pharmaceuticals division, said in an interview today. The company beefed up marketing by assigning the sales team responsible for the Herceptin breast cancer drug to also promote Avastin, while the group that sells the Xeloda therapy will promote it for use against colorectal cancer, he said.

“We focused on breast and then kind of lost steam on lung cancer a little bit,” Soriot said at Roche headquarters in Basel, Switzerland. “We’ll increase the promotional effort and I think we’re going to turn this around.”"

Sadly, though, this is not something that was unexpected, as many of us industry observers were secretly wondering how Genentech would fare once absorbed in the more conservative Roche system. One is very science based and the other is more corporate.

Just take a look at the two management teams and you get the big picture:

In the top picture, you see the Roche management team individually taken and in suits, but look like they have taken their ties off just for the photoshoot to make them a little less stiff and formal, perhaps.

In the bottom picture, the Genentech management team, taken as a team in fairly casual attire, with the CEO, Ian Clark, even wearing a fleece!

A tale of two very different cultures in one quick glance.

What impact does this have on the physicians? I asked around. Now, lung cancer doctors are fairly academic and science based, many also do translational research, for example. Underneath they are generally approachable, fun and always willing to answer questions or help people understand a complex topic. They're much more easy going than some of the other cancer specialties.

Which group do you think they would most likely mix with?

Therein lies the rub.

Corporate suits may look sharp, but do they engage and have fun with the scientists, or even understand their world? How much of a subtle impact might that have in the long run? While it is true that in the end, all marketing is ultimately about sales, the intangibles such as how you approach it and engage with customers along the way is often crucial to success.

Time to stop drinking the corporate Kool Aid and focus on the science, methinks.

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