Biotech Strategy Blog

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

Posts tagged ‘BCMA CAR T cell therapy’

Emerging key trends in hematologic malignancies

There is a peculiar irony to how cancer drug development works. Imagine decisions shaping billion dollar pipelines a decade from now tend to be made in the least glamorous corners of the world’s biggest conferences.

Cancer cells        Source: Dr. Cecil Fox, NCI

While the late-breaking and phase 3 trial readouts tend to command centre stage, the early signals worth paying attention to.

These include biology hunches, proof-of-concept datasets, even creative ideas too nascent for an oral slot, which often appear quietly on laminated boards in vast, cold hangars.

If you want to understand where hematology/oncology is heading then this is a good place to start to learn about five emerging trends in the field we’ve identified…

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How to achieve superior BCMA response rates without the liability of delayed MNTs

Killer T Cells surround a cancer cell Source: NIH

In the race for BCMA CAR-T dominance, we’ve long accepted a grim trade-off – to get industry leading response rates, you have to accept the risk of delayed movement and neurocognitive toxicities (MNTs).

Recent data from several groups are finally converging on why some constructs trigger these delayed events while others don’t.

The findings suggest the early belief that these issues were a result of higher expansion was likely off the mark…

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Next generation CAR-T cell therapies for the future

Putting new CARs in the spotlight

As we move on from second generation CAR-T cell therapies and CRISPR gene editing as well as a DNA to RNA shift, there’s a noticeable coming together of these modalities in novel next generation ideas now entering early stage trials in the clinic.

Inevitably some will fail, others will meet with mixed reactions on modest data, but a few will succeed and inspire the next round of innovative approaches.

Are there early signs of which products/companies might fall into each bucket?

Here we highlight fourteen examples to watch out for across biotechs and pharma alike while discussing some of the opportunities and challenges they may face…

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Talkin’ ’bout a Revolution

Chicago!

Sometimes innovation and revolution can happen in a quiet or stealthy fashion such that one may not notice until they’re in the middle of things.

Oncology R&D doesn’t stand still, it continually evolves as new and practical ideas or solutions to problems emerge, then are tested and finally (hopefully) implemented in the clinic.

The attrition rate is high, as what I call the cone of shame attests to this.

Over the ASCO weekend we saw two such examples of how change in the design of novel agents or cell therapy products can make an impact, in very different ways.

This latest post highlights one of them with two extended expert interviews and some commentary to boot…

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ASH Day 1 highlights and lowlights Part 2

The first day of ASH oral presentations brought some unexpected surprises from several quarters, both good and not so good.

In this second review of the highlights, we cover some important translational research, as well as various clinical studies in both AML and multiple myeloma.

The latter focuses on discussing some subtleties and nuances to watch out for in the BCMA CAR T cell space.  A number of people have been declaring ‘wins’ to different products across the board, but it’s way too early to call at this stage given phase 1 trials do not always predict what will happen in pivotal registration trials.  There are also some challenges to address along the way so we put these findings in context.

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Quest for the Holy Grail of Cell Therapy

CAR T cell therapy for solid tumours is the cancer new product development equivalent of the quest for the “Holy Grail.” It remains one of the cell therapy challenges of the coming decade.

Light inspires and illuminates

In this post we shine the light on one of the world’s leading cell therapy experts who is taking on that challenge.

Most of our posts are what is known in the business as “long-form” and this one is no exception; it’s over 7,000 words long and offers a veritable smorgasbord of insights into new cell therapies for blood cancers and solid tumours, novel targets, as well as future directions, including a company in stealth mode…

Curious to learn more about this important topic on cracking the code and the quest to find solutions?

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Going beyond BCMA as a target in multiple myeloma

With the startling news this morning that Poseida Therapeutics are abandoning their IPO plans and pursuing a different tack with a $142M investment from Novartis to fund clinical trials for their BCMA-directed CAR T cell therapy program in multiple myeloma, our attention is focused yet again on the highly competitive BCMA niche.

Poseida’s data was revealed at ASH last December and with an ORR of 63%, the initial efficacy was a bit lower than we have seen from rivals Bluebird Bio and Legend/JNJ, although the Penn/Novartis construct reported disappointingly lower responses in a small cohorts of patients, which may explain Novartis’s interest.

There are also other companies/products in this niche including GSK’s ADC, GSK2857916, and Amgen’s T cell bispecific, AMG 420, plus plenty of others with BCMAxCD3 bispecifics who have earlier skin in this increasingly highly competitive game.

Is BCMA enough though?  Is it really the answer to multiple myeloma or are there other approaches that might be better?

Putting new CARs in the spotlight

What of the future for CAR T cell therapies in myeloma beyond the initial generation 2.0 constructs?

We saw a vision for how this market might evolve and sought out some experts to learn more about what they are doing in this niche – what they had to say was really interesting.

After all, as Wayne Gretsky would say, don’t skate to where the hockey puck is (now) but where it will be… that’s a great analogy one cannot resist borrowing for the future of cell therapy in multiple myeloma.

In our latest article, we go beyond BCMA to explore where we think the field might be going and why a tunnel focus on BCMA might not be such a great thing…

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ASH18 Preview 3 – BCMA

We have covered BCMA-APRIL approaches in multiple myeloma for a couple of years now and it’s time for a much needed update and look at where this niche is.

The BCMA market is heating up

Beyond Bluebird’s bb2121 BCMA CAR T cell therapy, there are now a raft of different products across multiple companies including CARs, bispecific antibodies, and even ADCs.

What was a new target three years ago now is rapidly becoming a very crowded space indeed and the pressure will be on companies to differentiate their product in some way, otherwise they risk being a me-too or just another bowl of red chills…

As a new target is validated, it doesn’t take long for another ten companies to immediately try to capitalise on it in the ever increasing race to market with new product development.

Here, we take stock of where things are at.

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ASCO18 Day 1 Highlights

The calm before the #ASCO18 storm

Saturday 2nd June was the first day of ASCO for me this year, so continuing our annual tradition, we post a review of the daily highlights and topics or issues that caught our attention.

This can be useful for those of you sidetracked by off-site meetings and unable to actually get to the conference centre to hear talks – yes, it happens, more commonly than many realise!

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The Future of Multiple Myeloma

Happy New Year!

Immunotherapy treatment for multiple myeloma has been around for several decades, first in the form of stem cell transplantation, then augmented by the addition of IMiD immune modulation drugs such as thalidomide, lenalidomide or pomalidomide. In due course, along came immune checkpoint blockade in solid tumours and it was only a matter of time before they would be evaluated in hematologic malignancies, albeit with mixed results.

The proteasome inhibitors and IMiDs are unlikely to go away any time soon, but other targets have also emerged including CD38, SLAMF7/CS1, BCMA/APRIL, PD–1/L1 and a few others that are being currently investigated in the clinic.

Where does this leave us and what looks really promising?

In our latest thought leader interview undertaken at the recent American Society of Hematology (ASH) meeting in Atlanta, we asked a global expert for his candid views and were not surprised at some of the hard hitting comments that emerged from the in-depth discussion of several key issues…

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