Biotech Strategy Blog

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

Posts tagged ‘VEGF’

A phoenix rises from the ashesResilience in purpose and openess in strategic direction are key dual features in the DNA of strong biotechs which succeed in the long run and live to survive the roller coaster ride that is oncology R&D.

Setbacks are to be expected, but what matters more is not that they happen, but the mettle and toughness to deal with them over time.

There is no doubt Clovis Oncology encountered a major setback with the abandonment of rociletinib in lung cancer, while the rise of PARP inhibitors meant they were well placed with the rucaparib development.

Beyond these events, what next?

It’s time to take a bigger picture look at what’s happening with the pipeline and where they might be heading since there could be some surprises in store…

To learn more from our oncology analysis and get a heads up on the latest insights and commentary pertaining to ESMO20 virtual congress, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Scaling the ramparts in Real Madrido

It feels slightly surreal to be writing about this year’s annual ESMO confab instead of attending in person in Madrid, Spain.

While much of the time and attention at ESMO is usually focused on the major phase 3 readouts from various clinical trials, we will be covering these during the meeting as they are presented to avoid repetition since many of the topline company trial results have already been announced.

In this year’s conference Preview series, I wanted to take a step back and explore early new product development in several forms:

  • Biomarkers and potential new ways of predicting outcomes in development
  • Emerging novel targets of interest
  • Developmental therapeutics – trials and tribulations

This initial review will tackle some important developments pertaining to various biomarkers of interest.

To learn more from our oncology analysis and get a heads up on insights and commentary pertaining to ESMO 2020, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Looping across different types of analyses can yield intriguing and unexpected results

Not in Chicago It still feels surreal not to have been to windy city and back for the annual meeting at ASCO this year, such was the ongoing effect of the pandemic in the oncology world.

That said, the virtual meeting has produced some gems this year, including some very important findings many may have missed.

In our latest post meeting report we focus on both biomarkers and clinical findings.

We look at how there are various elements may interplay in unexpected ways, whether signatures from one trial are helpful in another, are there likely to be changes in treatment patterns as a result of data presented and where some emerging early signals might be useful.

One other aspect which crossed my mind was how a deep scientific approach used in one particular cancer might have potential applications in other tumour types with few somatic mutations present such as TNBC, prostate cancer or soft tissue sarcomas.

The results might produce quite different results, yet the process itself might be rather useful to consider…

To learn more from our oncology analysis and get a heads up on insights and commentary emerging from the ASCO meeting, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

In the third part of our ASCO GU coverage from San Francisco, which includes previews and post-match commentary, it’s time to turn our attention to renal cancer. This isn’t one disease, but a broad tumour type with multiple subtypes, some based on histology, with perhaps others to emerge down the road as we learn more about the disease and immune profiling.

There’s quite a bit to discuss this year, some of it quite complex and nuanced.

In the old days, much of the focus was on sequencing single agent TKIs in clear cell carcinoma, now it’s getting much more complex as scientists and researchers figure out combinations and regimen approaches, never mind what to do with the various histologies.

We walk readers through the latest information as we await the data presentations coming out tomorrow…

 

To learn more from our latest cancer conference coverage and get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Beyond Loxo’s RET inihibitor, LOXO–292 in RET+ cancers, there were quite a bit of other targeted therapy data to mull over at ASCO this year.

ASCO18 Gems from Poster Halls

We highlighted a few of these in our Preview series in terms of what to watch out for, so I wanted to take a moment and explore some of them in a more detail now that the data have been presented.

Did they live up to the initial promise or not? What can we learn from trial failures? Sometimes this can be even more valuable than positive trials.

To find out, we took a careful at some of the readouts and assessed what looked better or worse than expected to help readers make sense of the tsunami of data that were presented in Chicago.

Inevitably, some of the selections we chose are gems from the poster halls

To learn more and get a heads up on our latest oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Dr Max Wicha is the 2016 recipient of the AACR Distinguished Lectureship in Breast Cancer Research. At the 2016 San Antonio Breast Cancer Symposium (SABCS16) he gave his award lecture, “Targeting Breast Cancer Stem Cells: Challenges and Opportunities.”

SABC16 Dr Max Wicha Award Lecture

As the AACR press release notes, “This lectureship recognizes an outstanding scientist whose work has inspired or has the potential to inspire new perspectives on the etiology, diagnosis, treatment or prevention of breast cancer.”

Dr Wicha is a pioneer in the field of cancer stem cells, and is Director Emeritus of the University of Michigan Comprenhensive Cancer Center and a co-founder of OncoMed Pharmaceuticals (NASDAQ: OMED).

Targeting cancer stem cells is an area I expect we will hear a lot more about, particularly in breast cancer. Dr Wicha kindly spoke to BSB after his award lecture, which was one of my highlights of SABCS16.

In case you missed it, do check out the post from the 2016 EORTC-NCI-AACR Molecular Targets Symposium in Munich that featured Dr Mina Bisell (Berkeley), who was a previous recipient of the AACR Distinguished Lectureship in Breast Cancer Research award in 2012 (Link.)

This is the fifth in our series of expert interviews from the 2016 San Antonio Breast Cancer Symposium.

Subscribers can login to read more

This content is restricted to subscribers

It’s been very clear for over four years now that combinations were going to be necessary if we want to a larger number of deeper and more durable responses than can attained with monotherapy.  Gradually, we are starting to see early and very preliminary readouts with some of the trials in progress.

We are also learning very quickly that it’s going to be a case of #notalltumours and #notallsubsets.

ASCO 2016 Posters 2

Another very busy poster session at #ASCO16!

By this, I mean we obviously can’t take a one-combination-fits-all approach for all tumour types.

We need to be able to classify patients into more homogenous subsets and then devise different combinations or even sequences that address the underlying biology of both the cancer itself and also the tumour microenvironment.  That’s going to take a while to sort out, perhaps even years.

Let’s not forget though that in the meantime, we can gather information quite a few clues both preclinically, as well as from initial clinical studies.  Sometimes, after all, we even learn more from negative trials than positive ones. This is an area that is ripe for combinations with traditional targeted therapies, the question is which ones are promising and why?

We took a look at the landscape in SCCH&N and how this might evolve over time in the medium term, with future opportunities, that can be explored in rational combination approaches.

To learn more, subscribers can log-in or you can sign-up to join the ever-growing BSB club.

This content is restricted to subscribers

We’ve come a long way over the last two years in the oncology market, with several novel approaches approved, numerous major phase 3 trials evolving and a huge turnaround for many companies in terms of early pipeline activity.

ASCO 2016 Posters 3

The melée at the ASCO 2016 Poster Hall

Unfortunately, this also means that the tendency of lemming activity also increases in the rush to copy everyone else and not be left behind.  Just a couple of years ago, some industry friends grumbled that there were over 20 checkpoint inhibitors chasing them in development; they may be surprised to know that now there are nearly 70!  This is both unprecedented and unsustainable, and yet it’s also a function of the perceived success these agents have had on the cancer R&D landscape to date.  Everyone wants one for fear of being left behind… except that many are indeed way behind already.

You can imagine the tall guy on the left of the picture looking at his watch and wondering, “Ah so many new posters, so little time!”

Meanwhile, as the rate of approved cancer therapies increases, so does the inexorable march in terms of hyper-aggressive basket pricing.  I would argue that at some point, it no longer acceptable or even conscionable to change a premium or even market rate for drugs that give an incremental improvement of a mere 2 months of extra life.

Equally, one thing that many industry observers and the media love to do, and wrongly in my view, is to compare the individual drug prices on an annualized basis.  This is silly for several reasons:

  1. So far, not all patients are treated for a full year
  2. If patients are treated until progression and that happens early, then therapy is stopped
  3. What people should be looking at is the average treatment cost based on the length of therapy – some people will receive a few months and some much more than that
  4. What’s the true cost of a cure or remission to a patient and their family?
  5. How do we quantify the impact of the long lasting durable remissions?

These questions will become increasingly important as we see a more aggregated therapy approach emerge over the next few years.

By this, I mean that we are now going beyond monotherapy and even combinations; those trials have already long started and are the low hanging fruit that has been rapidly snapped up by the early players, as we eagerly wait for their data readouts.

If you have new agents coming-out of preclinical and into phase 1 development over the next year, there are a number of important questions to consider:

  • What are you going to do and where do you start?
  • How do you gain an edge when coming from (way) behind?
  • How do you develop unique positioning that could sustain your molecule in a sea of similar competitors?
  • Is it realistic to expect the 17th and 50th checkpoint to have equivalent efficacy as what went on before and will all of these seriously make it to market?

You can see now why even the FDA’s Dr Richard Pazdur was moved to grumble about the surfeit of me-toos here and company expectations that the FDA should consider them – it’s on a massive scale that we haven’t seen before.  For once I agree and empathize with him over that dilemma, it’s madness to think they will all be as good as pembrolizumab or nivolumab.

What we are starting to see emerge now is a surprising synthesis of ideas and a merging of disparate approaches. How will this affect oncology R&D over the next 1–5 years?

A couple of smart readers wrote in asking about these emerging trends, what have we identified so far, and where do we see the oncology space going in the near to medium term future. Now that AACR and ASCO are behind us, what can we learn about the new developments and where they all fit in the oncology landscape strategically?

To learn more about our strategic analysis, subscribers can log-in.

This content is restricted to subscribers

One of the (many) highlights for me at the recent annual meeting of the American Association for Cancer Research (AACR) was a “Meet the Expert” session presented by Professor George Coukos.

Prof George Coukos AACR 2016

Prof George Coukos AACR 2016

Professor Coukos is Director of Oncology at the University Hospital of Lausanne and Director of the Ludwig Institute for Cancer Research in Switzerland.

Ovarian cancer is becoming a fascinating battleground for cancer immunotherapy, with multiple challenges that must be overcome before we see improvements in outcomes, especially for women advanced disease.

The interview with Prof Coukos is a follow-on to the one we did on advanced ovarian cancer and checkpoint blockade at ECCO 2015 in Vienna with Dr Nora Disis (Link).

If you missed it, you can still listen to highlights in Episode 7 of the Novel Targets Podcast (Link).

After his AACR presentation, Prof Coukos kindly spoke with BSB and in a wide ranging discussion, highlighted some of the innovative clinical trial strategies he is working on to move the cancer immunotherapy field forward in ovarian cancer.

Subscribers can login to learn more about this important topic or you can purchase access.

This content is restricted to subscribers

Driving St Charles StreetcarAfter exploring the science behind chemotherapy improving T cell trafficking into the tumour yesterday – which is one of the key rate limiting issues that need to be addressed with immunotherapies such as checkpoint blockade – some obvious follow-up questions comes to mind:

  1. Does the compelling data in mice translate to humans?
  2. Can chemotherapy turn a cold tumour into a hot one?
  3. Will patients have improved outcomes as a result – or not?

It’s easy to dismiss traditional therapies in favour of appealing new developments, but what happens when we combine them?  Do we get additive effects, synergies or a negative impact?

As part of our ongoing AACR coverage, we explored this conundrum in the context of new data readouts, as well as the broader competitive landscape.

What we found was really interesting!

BMS, Merck and Genentech/Roche all have trials ongoing in the metastatic colorectal cancer space, with very different approaches being taken.  Does it matter?  Which one’s driving the bus?  We summarise these trials and offer some strategic insights on this niche.

To learn more, subscribers can log-in or you can sign-up…

This content is restricted to subscribers

Free Email Updates
Subscribe to new post alerts, offers, and additional content!
We respect your privacy and do not sell emails. Unsubscribe at any time.
error: Content is protected !!