CRSP Stock: Why It Fell Today

By Amit Chowdhry ● Oct 13, 2021
  • The stock price of Crispr Therapeutics AG (NASDAQ: CRSP) fell by over 6% pre-market today. This is why it happened.

The stock price of Crispr Therapeutics AG (NASDAQ: CRSP) fell by over 6% pre-market today. Investors are responding negatively to the company’s experimental blood cancer therapy results.

The company’s CAR-T cell therapy cleared cancer cells in 9 patients out of 24. But investors were hoping the treatment made from healthy donor cells would have worked better than existing therapies.

CARBON Trial Overview

The Phase 1 CARBON trial is an open-label and multicenter clinical trial evaluating the safety and efficacy of CTX110 in adult patients with relapsed or refractory B-cell CD19+ malignancies who have received at least 2 prior lines of therapy. And to date, the enrollment has been focused on patients with the most aggressive disease presentations, including diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), high-grade double- or triple-hit lymphomas, and transformed follicular lymphoma. 

The majority of the patients had Stage IV lymphoma and were refractory to their last line of therapy before entering the trial. 9 patients received prior autologous stem cell transplant. And patients who received prior autologous CAR-T therapy were not eligible.

As of the August 26, 2021 data cutoff, 30 patients with large B-cell lymphoma (LBCL) had been enrolled – of which 26 patients had received CTX110 with at least 28 days of follow-up and are included in the analysis. And only one enrolled patient did not receive CTX110. Three patients at the time of the data cut had less than 28 days of follow-up and were not evaluable for this analysis.

The patients were infused with a single CTX110 infusion following 3 days of a standard lymphodepletion regimen consisting of fludarabine (30mg/m^2/day) and cyclophosphamide (500mg/m^2/day). Patients could be re-dosed with CTX110 following disease progression. 

The primary endpoints include safety as measured by the incidence of dose limiting toxicities (DLTs) and overall response rate (ORR). And key secondary endpoints include complete response (CR) rate, duration of response and overall survival.


CTX110 was well tolerated across all dose levels. 

— There were no cases of Graft versus Host Disease (GvHD) and no infusion reactions to either lymphodepleting chemotherapy or CTX110.

— All cases of cytokine release syndrome (CRS) were Grade 1 or 2 per the American Society for Transplantation and Cellular Therapy (ASTCT) criteria and either required no specific intervention or were resolved following standard CRS management. Neither the frequency nor severity of CRS has increased in patients who were re-dosed with CTX110.

— The only case of Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS) was in the patient with concurrent HHV-6 encephalitis who was previously disclosed. There have been no cases of ICANS in any other patients treated at Dose Level (DL3) through Dose Level (DL4).

— Only 2 patients experienced Grade 3 or higher infections: the previously discussed patient with HHV-6 encephalitis, and one patient who developed pseudomonal sepsis that resolved in four days.

The emerging safety profile of CTX110 is positively differentiated from autologous CAR-T therapies that show high frequencies of severe CRS and ICANS, and from other allogeneic CAR-T therapies that require more toxic lymphodepletion regimens and can result in prolonged immunosuppression and increased risk of serious infections.

Clinical Activity

The data are shown below for the 26 patients that received CTX110 and had at least 28 days of follow-up. And the ORR and CR rates for patients treated at DL2 and above are shown both on an intent-to-treat (ITT) and modified ITT (mITT) basis. 

ITT includes all enrolled patients (n=24 at DL2 and above) whereas mITT includes only those patients who received an infusion of CTX110 (n=23 at DL2 and above). 

The dose-dependent responses and durable complete responses were seen with CTX110. And disease assessment was performed by investigator review according to the 2014 Lugano response criteria.

— A single dose of CTX110 at DL2 and above resulted in a 58% ORR and 38% CR rate on an ITT basis.

— Responses were seen in a variety of patients, including patients who had refractory disease, bulky disease, or who had progressed after prior autologous stem cell transplant.

— The data demonstrate the potential for CTX110 to produce durable remissions, as evidenced by a 21% six-month CR rate (4 of the 9 patients who achieved CR at Day 28, remained in CR at 6 months; 5 patients had not reached their 6-month evaluation point), which is in the range of durable remissions observed with approved autologous CAR-T therapies on an ITT basis.

— The data provide a strong rationale that consolidation dosing can improve on an already competitive profile for CTX110.

Based on this safety and efficacy profile, the company plans to expand into a potential registrational trial that incorporates consolidation dosing in Q1 2022. And in parallel, the company continues to advance the rest of its immuno-oncology portfolio and scale its manufacturing capabilities in its new state-of-the-art manufacturing facility in Framingham, Massachusetts.

Disclaimer: This content is intended for informational purposes. Before making any investment, you should do your own analysis.