Biotech Strategy Blog

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

Posts tagged ‘metastatic breast cancer’

The Therapeutic Index Dilemma

This is a story about how smart engineering and protocol innovation are reshaping T cell engager (TCE) – and potentially also antibody-drug conjugate (ADC) development.

To mask or not?

TCEs promised to bring the power of immunotherapy to solid tumours, but the story hasn’t been straightforward so far.

Despite compelling biology and mechanistic rationale, many promising agents have repeatedly stumbled over the same obstacle: a painfully narrow therapeutic window.

The culprit?

On-target/off-tumour effects triggering severe cytokine release and limiting dosing before efficacy can be fully realised. What if the solution wasn’t abandoning these targets altogether, but instead rethinking how we approach them?

Recent innovations in the HER2 space reveal three distinct strategies – clever sequencing protocols, avidity-driven engineering, and sophisticated masking approaches – which may finally crack this stubborn problem. The implications extend far beyond HER2 and could reshape development across multiple modalities, including ADCs.

For biotech strategists, the lessons here also challenge conventional portfolio wisdom about ‘over crowded targets’ and offer a roadmap for rescuing programs once deemed too toxic to pursue…

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Too Fragile to Succeed? Uncovering Hidden Weaknesses

When the crowd cheers the loudest, it’s often time to question the play.

Amid a wave of bullish investor enthusiasm for the Summit and BioNTech PD(L)1x VEGF bispecifics plus a raft of topo-I ADCs from China, the risks underpinning this rallying cry have been pushed to the shadows.

What if the foundations of the optimism are built on assumptions that don’t necessarily hold up to scrutiny?

In this analysis from the San Antonio Breast Cancer Symposium (SABCS), we unpack some of the overlooked vulnerabilities and present a case that might not win popularity contests, but could save companies and investors from costly missteps…

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Why Saturday at ESMO20 is like the Tour de France

Not in Madrid – Saturday was an incredibly busy day at ESMO20 with live oral presentations on multiple channels and the first of the Presidential Sessions.

TDF London 2014A conference can be like watching the Tour de France (TdF) which ends this weekend. If you’re standing on the route, you wait a long time for it to come along and then the peloton passes by in a flash. We experienced this in London back in 2014, where there was only a brief moment of time to capture the memory.

Like the TdF, cancer drug development is a team sport that takes place in a dynamic, competitive environment with moments of individual brilliance.

Yesterday at the ESMO20 virtual congress we listened to presentations, discussions, Q&A, interacted with experts, and put together two separate highlights posts, which captures the day so that BSB readers will not have to worry the Congress will pass them by.

When we were all going to live meetings, we anecdotally heard many people in Pharmaland used our conference coverage for writing their trip reports or getting a sense of the nuances around key trials, especially if they were in company meetings most of the time!

If you’re looking to get a picture of what was at ESMO20 then then do consider purchasing access. We put up a paywall seven years ago in September 2013 as a novel way to fund independent science journalism. Thanks to everyone who has been part of a journey that continues on.

In part 1 of our coverage of Saturday at ESMO20, we review and discuss some of the new developments in the breast cancer niche (catch up with part 2 covering key topics in lung, renal and urothelial cancers)…

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What’s new in advanced breast cancer?

This weekend in the oncology conference calendar saw the ESMO Breast meeting take place.

The event was originally planned as a live event in Berlin – sadly with the pandemic it ended up as a virtual meeting on Central European time, yet you can still imagine the Berlin bear welcoming everyone regardless of format!

This is a good time to take off we we left off last week with our SERD landscape review since there was some new clinical data presented in this niche, as well as segue to the ASCO meeting on Friday where other companies will also be showcasing their early data.

Aside from SERDs, there were plenty of other highlights and commentary to consider in advanced breast cancer.

Here we explore some of the findings and offer some context for at least one commercial showdown…

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Highlights and lowlights in HER2+ metastatic breast cancer at SABCS19

San Antonio River Walk

San Antonio – It’s time to switch horses and focus on the annual meeting of the San Antonio Breast Cancer Symposium (SABCS).

There have been many exciting developments in the HER2-positive niche and this meeting is no different in terms of new agents with promising (and some not so promising) to discuss.

We take a look at the tucatinib and trastuzumab deruxtecan data and put them in context because there are some nuances involved in both that need careful consideration.

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Targeting Breast Cancer Stem Cells

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.

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Still looking for a JPM17 Licensing Deal? How about a First-in-Class Drug for Metastatic Breast Cancer?

We’re kicking off the first in a mini-series of expert interviews from the 2016 San Antonio Breast Cancer Symposium #SABCS16 with a leading researcher who has discovered a first-in-class compound that shows preclinical promise in several cancers including multi-drug resistant metastatic breast cancer.

It has a novel mechanism of action: 

“Interestingly, it was the only molecule, out of the 150,000 we screened that seemed to work through this pathway.”

To go from “bench to bedside,” and take this drug into the clinic now requires funding beyond what academia can provide.

If you’re at #JPM17 and into early stage VC funding or are in pharma/biotech business development BD&L and are on the look out for an innovative new licensing/investment deal, this post is for you.

What makes this a great story is I heard that one “missing piece of the jigsaw” in working out the pathway through which the drug worked came from unrelated research presented at a seminar on wound healing in zebrafish!

As a 2013 article by Robin McKie in The Observer notes, zebrafish (Danio rerio) share 70% of our genes, which makes them pretty cool research models. They are also transparent.

Hearing this anecdote reminded me of my conversation with Dr William Pao that you can hear on Episode 3 of the Novel Targets Podcast where he astutely said:

 “You never know where things are going to lead, you just have to be able to take advantage of them.”

That could also be a metaphor for life.

Science is about making sense of connections and patterns, which is why funding of basic science is so important. A piece of work by one researcher can unlock a breakthrough by another in a totally unrelated area.

While I was doing this SABCS16 interview, I was also reminded of the story behind the development of enzalutamide, and how AACR past-president Dr Charles Sawyers pitched his UCLA drug discovery work to several major pharma companies, without success, until Dr David Hung at Medivation took the risk… and the rest is history.

What makes that story so surprising is at the time Dr Sawyers already had a track record of success with his work on the development of imatinib!

It was a privilege to talk with a senior scientist at #SABCS16 who has thought outside of the box, made scientific connections, and in the process developed a new drug that shows exciting preclinical promise.

Improving the outcome for cancer patients requires the translation of basic science into new products that enter clinical trials.

I do hope funding will be forthcoming to move this first-in-class drug into the clinic so that’s its potential can be fully evaluated.

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If you’re at #JPM17, it’s a great time to buy a sub to BSB and put it on your expenses!

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Checkpoint therapy update in metastatic breast cancer

Today the immunotherapy and related data flooding out of the annual meeting of the San Antonio Breast Cancer Symposium (SABCS) is pretty exciting!

Data was presented on a number of drugs including pembrolizumab, avelumab and atezolizumab, which put together with some recent publications, highlights some potentially exciting opportunities in this fast moving space.

Here, we explore the potential for checkpoint therapy combinations in TNBC, HER2 and even the ER+ subsets.  There’s a lot of new findings to take in and contemplate here.

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ESMO 2014 Preview on Breast Cancer

This last week saw the ASCO Breast Cancer Symposium in San Francisco, although very little caught my attention from a drug development point of view. Much of the attention seemed to be focused on surgery, genetic counselling and screening.

With the 2014 European Society of Medical Oncology (ESMO) conference in Madrid coming up fast in only 2 weeks time, it seems a good point to take a look at what’s on the slate there, since there are some important clinical trials being presented there with new data that we can expect to hear a lot more about.

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Companies mentioned: Roche/Genentech, GSK, Novartis, AstraZeneca, Medivation, Astellas
Drugs mentioned: Pertuzumab, trastuzumab, lapatinib, PI3K inhibitors, olaparib, enzalutamide

There are a couple of important breast cancer trials with data being presented for the first time at Madrid.

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Pfizer’s palbociclib data in ER+ breast cancer – hit or miss?

At AACR this weekend, Dr Richard Finn (UCLA) presented the much anticipated front-line phase II data for Pfizer’s CDK4/6 inhibitor, palbociclib (palbo) plus letrozole versus letrozole alone in ER+ HER2- breast cancer.

The PALOMA series of trials are designed to show that adding a specific CDK inhibitor to an aromatase inhibitor enhances efficacy and improves outcomes.

There are three metastatic breast cancer trials in all, with PALOMA–1 being the phase II study while PALOMA–2 and –3 are phase III randomised controlled registration studies aimed at confirming the initial phase II results in combination with letrozole and fulvestrant, respectively. In addition, palbociclib is also being evaluated in combination with standard endocrine therapy (PENELOPE-B) for certain early-stage breast cancers.

In short, an analysis demonstrated that the primary endpoint of progression free survival (PFS) was met, but the overall survival (OS) data was not significant at the time of the analysis.

What does this does this data mean and in what context should we look at the results?

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