Biotech Strategy Blog Posts | Biotech Strategy Blog

Is the Arvinas PROTAC Proof of the Pudding?

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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The Potential of CAR-NK Cells for Cancer Immunotherapy

This week the conference cycle continues with the annual meeting of the American Society of Gene and Cell Therapy (ASGCT) (Twitter #ASGCT20).

Due to the ongoing travel challenges and need for social distancing as result of Covid–19, one key annual immunology meeting originally slated for this month was AAI in Honolulu, which was sadly cancelled. Fortunately, ASGCT is being held as a live virtual meeting instead, so do check it out if you have a keen interest in this field.

One area we’re hoping to learn more about at ASGCT20 is cell therapy using natural killer (NK) cells. It’s an exciting and emerging area, which is attracting a lot of interest of late.

Those following the NK cell space will no doubt have seen the recent announcement of the collaboration between Kite/Gilead and Melbourne based oNKo-innate, co-founded by Prof Nick Huntington (@Dr_Nick_Bikes) and Dr Jai Rautella (Link to PR).

Other NK focused companies in the news include the licensing by Avectas of the CAR-NK cell therapy from Galway based ONK Therapeutics, founded by Prof Mike O’Dwyer (@MichaelodwyerMD) (Link to PR).

It’s definitely an exciting time to be an NK cell biologist!

In our ongoing series of expert interviews, we caught up with Prof Huntington from Melbourne to talk about the potential of CAR-NK cell therapies.

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Putting some colour on the TIGIT niche

Time for some additional colour commentary!

There has been some incredibly intense interest surrounding TIGIT as a new therapeutic target in oncology of late, to the point where some observers have been wildly claiming this is the new universal checkpoint everyone has been waiting for.

But is it?

It’s early days yet with little data presented from people with cancer, so at this point it could well be a bit of a stretch to find another anti-PD–1/PD-L1 equivalent, but this doesn’t mean there isn’t utility in seeing clinical activity in some tumour types, far from it.

In our latest post, we take a look at what’s coming up in the TIGIT niche, along with an interview from a company active in this niche.

What do the company have to say and how do they see this panning out?

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New directions in adenosine axis targeting

Making waves with new directions – there are many possible ways to go when considering targeting the adenosine axis

As we segue between our AACR and ASCO coverage, one topic that straddles both virtual meetings is targeting the adenosine axis. At AACR19, this pathway was very much front and square with some intriguing and controversial data presented, which caught many people by surprise.

Since then, several companies have opened new trials, others are completing enrollment and waiting for their data to readout before deciding upon next steps.

It’s a good time to take a look at what’s new in this niche and also see things differently through the lens of one company involved in the field. Yes, it’s time to share our latest expert interview from not one, but two, c-suite executives.

What are their perspectives (they are different), where do they see the field going and why?

In part one of the discussion we focus exclusively on adenosine targeting and how they see themselves differentiated from the crowd… it certainly makes for interesting reading!

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Flying high in the DDR oncology niche

Recently, PARP inhibitors have been back in the news for several reasons, including the publication of the olaparib (AstraZenca/Merck) advanced mCRPC data in the New England Journal of Medicine from the phase 3 PROfound trial and the announcement regarding achievement of the key secondary endpoint of overall survival. As Dr José Baselga quite rightly noted, this is very good news indeed because:

“Overall survival in metastatic castration-resistant prostate cancer has remained extremely challenging to achieve.”

We’ve rather more trial misses in this disease setting than successes from various therapies over the last few years including ipilimumab, PROSTVAC, alisertib, and atezolizumab, to name a few off the top of my head.

Related to mCRPC, let’s also not forget the upcoming PDUFA date later this month for Clovis’s rucaparib in the very same indication.

Not to be outdone on the PARP front, just a few days GSK received FDA approval for niraparib as first-line monotherapy maintenance therapy for women with platinum-responsive advanced ovarian cancer – regardless of biomarker status – based on the phase 3 PRIMA study presented at ESMO last year and simultaneously published in the NEJM. Recall that the majority of women (51%) had homologous-recombination deficiency (HRD) and this subset saw the greatest benefit.

Flying high in the DDR space?

We have now seen clinical benefit in the PARP inhibitors in four tumour types driven by DNA damage repair (DDR) deficiencies, namely ovarian, breast, pancreatic, and prostate cancers.

How do we go about extending the concept of DDR in terms of the biology of other tumour types?

A number of related pathway targets have been investigated, including ATM/ATR, Chk1, Wee–1 and others, with mixed success.

It’s not the nature of oncology R&D to stand still, however; what if we could turn things on their head and think creatively about the problems still to be addressed?

One particular new company to the PARP space is doing just that… so what are they doing and what’s different about their approach?

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Novel anti-cancer agents to watch out for

A saying for the ages from Albert Einstein

Oncology R&D is – perhaps surprisingly – very much like the bicycle analogy Albert Einstein described.

There are many ways we can see this happening at meetings such as AACR and ASCO as companies struggle to finesse the therapeutic window and balance efficacy with toxicity, for example.

Or how about finding creative ways to extend and broaden a particular drug class?

Another approach might be to take an entirely different angle to tackling a tumour type by targeting an antigen few others are pursuing. Just because the herd is going in one direction doesn’t mean you should follow them down the same path as well.

Then there’s switching modalities, orthosteric versus allosteric inhibitors, or how about some med chem magic where researchers seek to enhance the good properties and minimise the weaknesses while still hitting a target selectively?

All of these methods require some kind of balancing act if you want your pipeline to move forward rather remain still or fall over in the doldrums.

Today’s post has all of this and more – there are some novel compounds and targets, emerging biotechs and big pharmas, as well as innovative thinking to make a difference. Several of these agents are first-in-class, which means the rest of us can learn much from the lessons they have shared.

What’s not to like?

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Standing out from the crowd

What stood out at AACR20?

With every cancer conference ‘attended’ – this includes the ubiquitous virtual meetings these days – I usually ask myself a couple of simple, yet key questions:

Did we see any promising new targets or agents in early development emerge?
Did any one talk or concept stand out from everything else?

Sometimes the answer is an emphatic ‘no!’ to both, sometimes a ‘maybe’ to either, while at other times, one thing clearly stands out head and shoulders from the rest.

At AACR20, one particular development stood out clearly for me as being novel and innovative, as well as encouraging on several fronts, so let’s take a look at what’s different about it and why a KOL we interviewed was quietly excited…

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Postcard 2 on Adoptive Cell Therapies from the AACR20 Virtual Meeting

The American Association for Cancer Research (AACR) is to be congratulated on turning their annual in-person meeting into a virtual meeting at short notice.

With over 60,000 registered attendees, the meeting is a success and has set the standard for others to follow this year. While we all miss the opportunity to meet and network in-person, a virtual meeting does democratize access to science for scientists and researchers who can’t afford to travel or attend every year and we hope that live-streaming will continue in 2021 and beyond.

Since the sessions are available to watch for free on demand, we’re not repeating the data but like a postcard are instead focusing on what stood out for us, adding some pertinent commentary or context, as well some of our key take homes from a cancer new product development perspective.

Whether you agree, disagree, or thought differently about the presentations, we’re here to provoke thinking and critical discussion.

In this latest postcard from AACR20, we’re focusing on highlights from the adoptive cell therapy session taking place earlier today.

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Postcards from Day 1 of AACR20

Reflections on Day 1 of the AACR20 Virtual Meeting Part 1 – through a series of postcards

For cancer conferences, 2020 will be the year of the Virtual Meeting. The easy going world as we knew it just a few months ago is suddenly no longer.

We already know that many countries will be maintaining social distancing until at least the end of the year and perhaps longer into 2021. In others, a mandatory 14-day quarantine already in place for people entering the country will likely deter travel. Who wants to travel to a conference – even presuming it is going ahead – only to have to stay at home for 14 days afterwards?

The net result is that virtual meetings are likely here to stay for the duration and in the next few months we’ll see how organizations such as AACR, ASGCT, ASCO, and EHA produce them.

As of yesterday, there were 47,000 registered attendees for part 1 of the AACR virtual meeting, which is largely focused on early clinical trials.

What were some of the take-homes from Day 1 at the AACR20 virtual meeting?

We listened to many of the sessions and in this post share what stood out for us.

If you missed it, do check out our AACR20 Previews and ongoing coverage plus we will be rolling out additional in-depth posts once the meeting is over.

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One swallow does not a summer make

There’s a lot of hype and noise of late surrounding the Iovance TIL therapy licensed under a CRADA from the NCI based on Dr Steven Rosenberg’s work.

Another Brick in the Wall for TIL therapies?

A few years ago many acadenics vehemently argued that TILs wouldn’t go much further than metastatic melanomas (cutaneous or uveal) and certainly there were dramatic responses seen from the before, during and after photos, as anyone who attended AACR in 2013 will attest.

Seven years on, the TIL topic is back in fashion again – is the hype justified or are the plaudits based more on a wing and a prayer?

We have some firm views to share on this topic…

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