Ash 2021 preview – as competition grows Autolus monetises

Several cell therapy presentations will vie for attention at Ash, though today the spotlight falls on Autolus.

With $150m of funding secured from Blackstone this morning the heat is off Autolus to present earth-shattering obe-cel data at Ash. Given that Autolus was down 40% year to date the bull case is that Blackstone has already seen what it likes in the data, and has effectively called the bottom.

Then again, it is hard not to be disappointed by Autolus’s fall from a company working on cutting-edge cell therapy to one seeking to commercialise a run-of-the-mill CD19 Car. Other Ash presentations give a clue about the group’s future competition, though for now perhaps the best thing is that obe-cel has been monetised.

For a $100m equity stake plus $50m in cash Blackstone secures an interest in obe-cel, will receive a single-digit sales royalty, and will pay a further $100m in milestone-based development financing. The private equity group has also secured a seat on Autolus’s board.


This might be enough for some to see this as a prelude to a takeout, though a $50m equity stake implies extremely early days. Still, it cannot be disputed that PE usually strikes when equity prices hit rock bottom, and Autolus has had quite the fall from grace.

When the Ash abstracts went live last Thursday Autolus analysts focused on the Felix trial of obe-cel, an autologous anti-CD19 Car with a novel binding domain, in adult ALL. However, the placeholder abstract gave away no data, discussing the automation of an academic manufacturing process.

Thus all investors have to go on for now is Autolus’s word – plus Blackstone’s implied endorsement – that Felix is seeing one-month response rates in line with those in the academic Allcar19 trial, which showed 85% ORR in 20 subjects, no serious cytokine release and a 15% rate of neurotoxicity.

This might be an improvement over the likes of Yescarta, but an autologous CD19 Car hardly moves the needle today. Evaluate Pharma lists 49 such assets in phase 1 and 2 trials alone, for instance.

Selected CD19-directed cell therapy presentations
Project Company Trial Abstract Cutoff Detail
Yescarta Gilead Zuma-7 2 (plenary) 18 Mar Median EFS 8.3mth vs 2.0mth for SoC (HR=0.398; p<0.0001)
Breyanzi Bristol Myers Squibb Transform 91 ? Median EFS 10.1mth vs 2.3mth for SoC (HR=0.349; P<0.0001)
Obe-cel Autolus Felix 477 ? Adult ALL, abstract is on manufacturing process
YTB323  Novartis NCT03960840 740 16 Apr <2-day manufacture: At DL1 25% 3mth ORR (n=4), at DL2 75% 3mth ORR (n=8)
PBCAR0191* Precision NCT03666000 650 2 Aug CD19+ ALL: day ≥28 CR rate is 33% (2/6) in DL3/4a and sLD, 80% (4/5) in DL3/4a with eLD and 75% (3/4) in DL4b with sLD
ALLO-501A* Allogene Alpha-2 649 9 Jul Discusses consolidation therapy; programme on clinical hold
FT596** Fate NCT04245722 823 25 Jun 53% ORR (n=17), notes retreatment
DL=dose level, sLD=standard lymphodepletion, eLD=extensive lymphodepletion. *allogeneic; **allogeneic NK cell therapy; all others are Car-T. Source: Ash.

As ever, Ash offers an insight into more cutting-edge cell therapy approaches, notwithstanding the fact that Yescarta and Breyanzi’s respective second-line lymphoma trials, Zuma-7 and Transform, take centre stage thanks to a plenary and key oral presentations.

These will be key to determining whether Car-T can move towards front-line lymphoma therapy, and the absence at Ash of the corresponding Belinda study of Novartis’s Kymriah, which failed, will disappoint those who wished to delve into the differences between the trials.

Novartis, however, is presenting two early-stage clinical abstracts, concerning the anti-CD19 Car YTB323 and the BCMA-directed PHE885, that should generate lots of interest. This is because they concern projects that Novartis claims to be able to manufacture in two days, a potential game-changer for autologous cell therapy.

Like most Ash abstracts the data described are from an early cutoff, but they could validate the company’s T-Charge technology, which reduces ex vivo culture time to 24 hours and preserves naive and stem cell memory T cells in the final product.

Among other CD19-directed cell therapy approaches investors will also focus on Fate’s Car-NK project FT596. At Ash 2019 this had only preclinical data and a year ago there was a sole case report, but this year’s abstract details 17 patients, and response durability should be a major focus at Ash.

The FT596 abstracts cites the potential for retreating relapsed patients. Also ploughing the retreatment furrow will be the allogeneic player Allogene, though investors will focus primarily on the hold the FDA has placed on all its clinical work.

Selected multiple myeloma presentations
Project Mechanism Company Trial Abstract Cutoff Detail
Cilta-cel BCMA Car-T J&J/Legend Cartitude-1 549 11 Feb 98% ORR (n=97), 6 treatment-related deaths, 5 treatment-unrelated deaths
PHE885  BCMA Car-T Novartis NCT04318327 3864 1 Apr <2-day manu: 100% 1mth ORR (n=6)
P-BCMA-101 BCMA Car-T Poseida NCT03288493 3858 30 Jun ORR 72% in Rituxan/Revlimid combo (n=90?)
CYAD-211 BCMA Car-T (shRNA allo) Celyad Immunicy-1 2817 29 Jul ORR 25% (all PRs, n=8)
REGN5458  BCMA bispecific Regeneron NCT03761108 160 10 Jun 73% ORR at 90mg & 200mg (n=17), high end of dosing
TNB-383B (ABBV-383) BCMA bispecific Abbvie NCT03933735 900 10 May Ex Teneobio (acq by Amgen), ≥40mg Q3W ORR 79% (n=24)
RO7297089 BCMA bispecific (via CD16) Roche NCT04434469 2755 30 Apr 1/18 PR suggests just hints of efficacy
MCARH109 GPRC5D Car-T MSKCC NCT04555551 827 28 Jul 83% ORR (n=12), 2 responses unconfirmed
Talquetamab GPRC5D bispecific J&J/Genmab NCT03399799 158 19 Jul ORR 70% (n=30) at 405µg/kg weekly; 69% in 13 subjects last year
Cevostamab  FcRH5 bispecific Roche NCT03275103 157 18 May 158 pts now efficacy evaluable, vs 51 a year ago
Source: Ash.

Meanwhile, in multiple myeloma, BCMA-targeting competitors will be squaring up to Johnson & Johnson/Legend’s Cartitude-1 study of cilta-cel, whose Pdufa date was recently delayed by three months to February 28, 2022.

But perhaps, following a recent trend, there will again be more interest in bispecifics than Car-T, and in follow-ons to targeting BCMA, a crowded space. Here the first ever clinical data on Memorial Sloan Kettering’s Car-T asset MCARH109, which targets GPRC5D, are keenly awaited, and the early abstract data look impressive.

An update on Johnson & Johnson/Genmab’s talquetamab, an anti-GPRC5D bispecific that impressed last year, should also be on investors’ radar. Autolus was right to monetise obe-cel when it had the chance, but it has little time to lose when it comes to putting the cash to use.

Selected CD20-directed T-cell engagers
Project Company Trial Abstract Cutoff Detail
Mosunetuzumab Roche NCT02500407 127 (press) 15 Mar ≥3L FL: 79% ORR (n=90) [68% ORR at Ash 2020]
Glofitamab Roche NCT03075696 128 18 May r/r FL: ORR 81% (n=43) for monoRx [ORR 64% in NHL at Ash 2020]
Plamotamab Xencor/J&J NCT02924402 2494 1 Jul r/r NHL: ORR 43% (n=53) [39% ORR at Ash 2019]
Epcoritamab Abbvie/Genmab Epcore NHL-1 1413 15 Jul SC dosing, but poster is on CHOP combo in 1L NHL
Igm-2323 IGM Biosciences NCT04082936 132 30 Apr 35% ORR (n=23)
Source: Ash.

The Ash conference is due to take place virtually, and in person, on December 11-14 in Atlanta, Georgia.

Evaluate Vantage's Jacob Plieth spoke to the biotech investor Brad Loncar in advance of ASH about the meeting's themes: 

Related Topics

Share This Article