Crispr: nice valuation, but where’s the clinical trial?

It will have escaped few people’s attention that the combined valuation of the three listed Crispr companies more than tripled over the past year, and now stands at nearly $6bn. And yet, despite the promises, none has even a clinical trial to show for it.

The latest disappointment came yesterday, when Crispr Therapeutics – which claims to be the leader by timeline – said the US FDA had slapped a clinical hold on its Vertex-partnered lead. Even after opening down 8% today this company is still worth $3bn; there is just one enrolling western trial of a Crispr-based therapy, and ironically it does not feature any of the three listed players (see table below).

This study is being run by the private group Tmunity Therapeutics, and strictly speaking does not involve a Crispr-based gene therapy. Rather, it tests the ex vivo modification of autologous NY-ESO-1-directed T cells to edit out PD-1 and their endogenous T-cell receptors; these cells are then reinfused into a patient to stimulate an anti-tumour response.

Even that was a long time coming. The NIH’s recombinant advisory committee had given Tmunity the go-ahead in mid-2016, but it took a year before an IND was filed; according to the trial only started enrolling patients this month, and it is not clear whether any have yet been treated.


Crispr Therapeutics managed to file its own US IND last month, but according to yesterday’s statement this has been set back by the FDA raising “certain questions”. Investors will note that it is only months since a scientific paper suggested that most people might be immune to Crispr Cas9 (JP Morgan interview – Crispr hopes its CAR will overtake Cellectis, January 12, 2018).

Editas, at whose JP Morgan presentation this issue was raised, still maintains that the IND for its first project, against a form of inherited blindness, will be filed in mid-2018; if this happens it will come six months later than originally planned.

Meanwhile Intellia, the last of the listed Crispr trio, has yet to undertake IND-enabling activities. It had earlier planned to begin these in mid-2018, but its last presentation simply stated 2018 as the timeframe.

Selected US-focused Crispr players
Project Sponsor Status Detail Trial ID
NY-ESO-1 eTCR Tmunity Recruiting TCR-deleted, PD-1-deleted T cells, various cancers NCT03399448
CISH-inactivated TILs NCI Not yet recruiting Gastrointestinal cancers NCT03538613
CTX001  Crispr Therapeutics/Vertex IND on clinical hold Sickle cell disease (EU β-thalassaemia study to start H2 2018) (none)
EDIT-101 Editas IND filing mid-2018 Leber congenital amaurosis (none)
CTX101 Crispr Therapeutics IND filing end 2018 Anti-CD19 CAR-T (none)
ATTR programme Intellia/Regeneron IND-enabling trials 2018 Transthyretin amyloidosis (none)
P-BCMA-ALLO1 Poseida/J&J Preclinical Allogeneic CAR-T, using Cas-Clover (none)
Not yet defined Beam Therapeutics Preclinical Claims to be able to make single-base corrections (none)
Source: & company materials.

With the US timeline slipping so badly it might come as a surprise that the only other near-term Crispr trial has nothing to do with industry.

This is to be run by Dr Steve Rosenberg’s surgery branch at the NCI, and involves autologous tumour-infiltrating lymphocytes with the gene coding for CISH, the cytokine-inducible SH2-containing protein, edited out. A entry that appeared just this week says this study should start in June. also lists six Crispr trials actively enrolling patients in China. There are likely many more that have not been filed with the US registry, and thanks to a favourable regulator and relatively low chances of litigation China might lead western markets in Crispr for some time.

Then there is a broader problem, namely a long-running Cas9 patent dispute between the Broad Institute and the University of California, Berkeley. Judging by the slow pace of development, however, intellectual property is not the first thing Crispr-focused investors have to worry about.

Disclosed clinical trials involving Crispr in China
Project Sponsor Status Detail Trial ID
CCR5-modified CD34+ cells Peking University Recruiting HIV-infected subjects with haematological malignances NCT03164135
CD19 CAR-T Chinese PLA General Hospital Recruiting Allogeneic, CD19+ve leukaemia & lymphoma NCT03166878
Dual-specificity CD19/CD20/CD22 CAR-T Chinese PLA General Hospital Recruiting Allogeneic, leukaemia & lymphoma NCT03398967
PD-1-knockout T cells Anhui Kedgene Biotechnology Recruiting Oesophageal cancer NCT03081715
PD-1-knockout T cells Chengdu Medgencell Recruiting NSCLC NCT02793856
PD-1-knockout EBV-CTLs Nanjing Uni Medical School Recruiting EBV-associated malignancies NCT03044743
PD-1-knockout T cells Cell Biotech Not yet recruiting Muscle-invasive bladder cancer NCT02863913
PD-1-knockout T cells Cell Biotech Not yet recruiting Castration-resistant prostate cancer NCT02867345
PD-1-knockout T cells Cell Biotech Not yet recruiting Renal cell carcinoma NCT02867332

Share This Article