Biotech Strategy Blog

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

Posts tagged ‘PROTACs’

Every once in a while a completely new modality comes along, which turns things on their head and changes how we think about cancer drug development.

The first chemotherapy, the first TKI, the first monoclonal antibody or bispecific antibody… the list goes on.

Each one creates a new race and bunch of companies and molecules quickly follow the trendsetter.

How about the first protein degrader to show initial evidence of clinical activity in men with a particular type of cancer?

This is exactly what Arvinas have done with their novel PROTAC molecule, ARV–110, in men with advanced metastatic castration-resistant prostate cancer who have received prior hormonal therapy.

What can we learn from the data due to be presented at ASCO and from what lens of the kaleidoscope should we be really be looking at? To find out more, I spoke to an expert in this niche, the scientist who developed the technology, Dr Craig Crews.

What he had to say and how he got there is well worth listening to. I doubt doubt he quietened a few sceptical researchers along the way who likely thought it wasn’t possible to do in patients having heard a few of them in Q&A sessions at various conferences over the last five years. One of them (who will remain nameless) when asked what he thought of the idea actually scoffed at me in a coffee break, “It’s a preposterous idea – it’s fine in mice I suppose, but it’ll never be done in patients, mark my words!”

*Coughs*

During my convivial chat with Dr Crews, I was remembering the moment from the past and wondering what he might be thinking now… to the brave and creative scientists go the spoils of victory.

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ASH19 Targeted Therapies Preview: This year’s ASH in Orlando is very much dominated by new developments on the immunotherapy front in terms of both T and NK cell therapies, with some passing interest in BTK inhibitors as well.

It’s not always sunny in Florida…

What about targeted therapies and the science behind those developments?

It was not that long ago that these were the main lifeblood of the meeting across many, if not most, hematologic malignancies. How times have changed!

That said, outside of the CARs (T and NK cells), as well as bispecific immunotherapies, and BTK inhibitors there are still some gems to be found amongst the rest of the ASH19 abstracts.

Here we highlight an additional 10 abstracts involving early pipeline areas that encompass some novel targets, new combination approaches, or emerging science.

Please note that the novel targets can take the form of classic targets or IO ones since they didn’t fit in the prior ASH Preview topics already reviewed under separate cover

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Time for some reflection

Before we get to the World Congress in Lung Cancer (WCLC) taking place this weekend, I want to take a moment to reflect on some of the things we have learn over the last few weeks.

It’s time for a reader mailbag as we answer reader questions on the recent MYC mini-series, as well as covering bromodomain inhibitors (what’s going on there?) and discuss a new PROTAC compound in early development that looks quite interesting.

We also explain why that is the case…

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Cambridge – Amongst the historic colleges and cloistered walls of one of the world’s oldest universities there is pioneering research going on, and not only that, it’s potentially being translated into potential new cancer treatments.

Dr Laura Itzhaki (Twitter: @LauraItzhaki) is professor of structural pharmacology at the University of Cambridge. She is also founder and chief scientific officer of a start-up biotech company, which is focused on the discovery and development of a new class of drugs called polyproxin molecules.

University of Cambridge

Prof Itzhaki’s research is the basis of the science and intellectual property behind PolyProx Therapeutics, and the company earlier this year received £3.4 million in seed financing. This may not be a huge deal in US terms, where we’ve seen some truly mind blowing Series A financing rounds for start-up cell therapy companies, but it’s not inconsequential in UK terms. We’ve also seen with today’s £100M Series B funding announcement for Stevenage based Achilles Therapeutics (whom we profiled a year ago) that early stage UK companies can indeed go on to big things.

Basic science is the backbone of cancer research – let’s not forget that translating the new discoveries into the clinic is how new products are developed and it’s exciting to see an increasing number academics take the next step on that journey.

During a visit to Cambridge this year, Prof Itzhaki kindly spoke with BSB about her research and the direction PolyProx hopes to travel. It’s very early stages for the company, yet it’s a story we very much look forward to following, and one I expect we will hear more from, as other companies look to partner with them in the future….

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The B-cell maturation antigen (BCMA) is an oncogenic protein target relevant to multiple myeloma that we have been following for a while on BSB, including an expert interview with a global myeloma KOL at ASH last December as part of a wide ranging discussion and deeper look at the Future of Multiple Myeloma.

San Diego

This weekend I was following a myeloma workshop where quite a bit of teasing early data was presented that may give us clues about what’s likely to be interesting at ASH18.

I wasn’t the only one doing this judging by a raft of reader questions that came in, particularly on the topic of BCMA and other emerging targets in this disease.

Is one BCMA better or worse than another? Will antibodies take a BiTE out of the CAR-T cell therapy noise? We take a careful look at these issues to explore what’s what and what really matters in this niche.

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The BET Bromodomain market is a meaty epigenetics topic we have followed for several years now, including a look at the space back in 2013 on the old Pharma Strategy Blog (Link). The last update on this was ironically at AACR last year when we discussed MYC and bromodomains (Link).

Nawlins Mardi GrasIn a remarkable tale of two cities in real life, two companies we discussed in those posts – Constellation Pharma and Tensha Therapeutics – have had markedly different fortunes since then. Roche decided to end their collaboration with the former and went on to acquire the latter instead.

Since we first wrote about bromodomains and BET inhibitors, the niche has exploded in a wildly stunning way… More drugs in the pipeline, more tumour targets being explored, and even novel combinations being evaluated preclinically for synergistic or additive effects. Even I was surprised by how competitive this niche has become based on the offerings at AACR this year.

With all the wealth of new data at the AACR annual meeting and also some other recent presentations I’ve attended elsewhere, it’s time for a more in-depth look at the BET/Bromodomain landscape.

Who are the new players, which tumour targets are now being evaluated, which combinations might be useful?

A word to the wise – this is neither a nerdy science post nor a comprehensive literature review – instead we take a look at the emerging landscape from a new product development perspective.

Science has been absolutely critical to success in all of the cancer therapeutics from targeted therapies to immunotherapies that have emerged in the last decade.

It really doesn’t matter whether you come from a marketing and commercial organisation or the investment community – if you want to make great decisions, you need to understand the basics of the science underpinning the R&D, where the strengths and weaknesses are. The alternative is play Roulette and put everything on Black 11 as a euphemism for whichever company/product/target you have an interest in.

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