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Vertex Pharmaceuticals (VRTX) and Crispr Therapeutics (CRSP) announce presentation of new data on exa-cel, formerly known as CTX001, from CLIMB-111, CLIMB-121 and CLIMB-131 highlighting the potentially transformative profile of this investigational therapy for people with transfusion-dependent beta thalassemia or severe sickle cell disease and provided additional program updates. The data presented at the European Hematology Association Congress are from 75 patients - 44 with TDT and 31 with SCD - with follow-up ranging from 1.2 to 37.2 months after exa-cel dosing. Of the 44 patients with TDT, 26 had beta-zero/beta-zero or other beta-zero-like severe genotypes. Forty-two of 44 patients with TDT were transfusion-free with follow-up ranging from 1.2 to 37.2 months after exa-cel infusion. Two patients who were not yet transfusion-free had 75% and 89% reductions in transfusion volume. TDT patients had substantial mean increases in fetal hemoglobin and corresponding increases in mean total hemoglobin with mean total Hb levels increasing to greater than11 g/dL by Month 3 and maintained thereafter. All 31 patients with severe SCD characterized by recurrent vaso-occlusive crises were free of VOCs after exa-cel infusion through duration of follow-up, with follow-up ranging from 2.0 to 32.3 months. SCD patients had mean HbF of approximately 40% by Month 4 and maintained thereafter. The safety was generally consistent with myeloablative conditioning with busulfan and autologous stem cell transplant. All patients engrafted neutrophils and platelets after exa-cel infusion. Among the 44 patients with TDT, two patients had serious adverse events considered related to exa-cel. As previously reported, one patient had three SAEs considered related to exa-cel, hemophagocytic lymphohistiocytosis, acute respiratory distress syndrome and headache, and one SAE of idiopathic pneumonia syndrome that was considered related to both exa-cel and busulfan. All four SAEs occurred in the context of HLH and have resolved. One patient had SAEs of delayed neutrophil engraftment and thrombocytopenia, both of which were considered related to exa-cel and busulfan, and both SAEs have resolved. Among the 31 patients with SCD, there were no SAEs considered related to exa-cel. Following ongoing discussions with regulators, the clinical trial protocols for CLIMB-111 and CLIMB-121 were amended to incorporate feedback on the primary endpoints for regulatory submission. Specifically, the primary endpoint in CLIMB-111 for TDT has been amended from proportion of subjects achieving transfusion reduction after exa-cel infusion to proportion of subjects maintaining weighted average Hb greater than or equal to9 g/dL without red blood cell transfusions for at least 12 consecutive months after exa-cel infusion. The primary endpoint in CLIMB-121 for SCD has been updated from proportion of subjects with HbF greater than or equal to20% after exa-cel infusion, to proportion of subjects who have not experienced any severe VOCs for at least 12 consecutive months after exa-cel infusion. Both clinical trials are now in Phase 3 and are fully enrolled. All patients will have the opportunity to join CLIMB-131, a long-term follow-up study, after completing participation in the initial studies. In line with the company's strategy of developing therapies for patients of all ages, two additional Phase 3 studies of exa-cel have begun. Earlier this year, the Independent Data Monitoring Committee met to review the data in adults and adolescents and endorsed expanding into younger pediatric patients. CLIMB-141 and CLIMB-151 are Phase 3 open-label trials designed to assess the safety and efficacy of a single dose of exa-cel in patients ages 2 to 11 years with TDT or SCD, respectively. The trials are now open for enrollment and currently enrolling patients ages 5 to 11 years and will plan to extend to patients 2 to less than 5 years of age at a later date. Each trial will enroll approximately 12 patients. Patients will be followed for approximately two years after infusion. Each patient will be asked to participate in CLIMB-131, a long-term follow-up trial. Vertex also presented three additional abstracts on the burden of disease in sickle cell disease and beta thalassemia at the EHA Congress.

Vertex Pharmaceuticals announced that five scientific abstracts on the company's portfolio of cystic fibrosis medicines will be presented at the European Cystic Fibrosis Society's 45th European Cystic Fibrosis Conference held June 8-11, 2022, in Rotterdam, the Netherlands. Vertex will present the first analysis of data collected in the U.S. CF Foundation Patient Registry of over 16,000 people with CF treated with TRIKAFTA for an average of nine months. This first interim analysis of an ongoing five-year post-authorization study showed that real-world treatment with TRIKAFTA was associated with improved lung function and a 77% reduced risk of pulmonary exacerbations compared to pre-TRIKAFTA baseline, as well as an 87% lower risk of lung transplant and a 74% lower risk of death, compared to the historical 2019 U.S. CFFPR population. No new safety concerns were identified. Vertex will also present data comparing the annual rate of lung function change in people with CF ages 12 years and older with two F508del mutations or one F508del mutation and one minimal function mutation treated with TRIKAFTA in pivotal studies and an open-label extension study compared to propensity-score matched historical CFTR-modulator-untreated controls from the U.S. CFFPR. Results show that TRIKAFTA demonstrated on average no decrease in ppFEV1 over a two-year period in this population, in contrast to declines seen in the matched controls. The analysis indicates that treatment with TRIKAFTA has a significant impact on the trajectory of CF lung disease. Additionally, Vertex will present data from a long-term real-world study demonstrating that initiating KALYDECO early in life preserves lung function to a greater extent than if KALYDECO is initiated at an older age. These results show the importance of early initiation of KALYDECO for eligible patients.

Vertex Pharmaceuticals announced the U.S. Food and Drug Administration, FDA, has granted inaxaplin, VX-147, Breakthrough Therapy Designation, BTD, for APOL1-mediated focal segmental glomerulosclerosis and the European Medicines Agency, EMA, has granted inaxaplin Priority Medicines, PRIME, designation for APOL1-mediated chronic kidney disease. Inaxaplin is the first investigational therapy aimed at treating the underlying cause of AMKD. Vertex now holds three of the approximately 70 non-oncological PRIME designations granted to date, including its two PRIME designations for exagamglogene autotemcel, formerly known as CTX001, one for transfusion-dependent beta thalassemia and one for sickle cell disease. In the US, this is the ninth breakthrough therapy designation granted to Vertex across its portfolio programs.

Vertex Pharmaceuticals provided additional data on patients dosed in Part A of its Phase 1/2 clinical trial of VX-880, an investigational stem cell-derived, fully differentiated pancreatic islet cell replacement therapy for people with T1D with impaired hypoglycemic awareness and severe hypoglycemia. As reported last month, both patients treated with half the target dose of VX-880 achieved glucose-responsive insulin production, improvements in glycemic control and reductions in exogenous insulin requirements. The data presented today show significant increases in the blood glucose time-in-range compared to baseline, following treatment with VX-880. Time spent in target range is a clinically important metric in diabetes management that reflects the amount of time a patient's blood glucose level is measured in the desired, target blood sugar range. The accepted American Diabetes Association/European Association for the Study of Diabetes target for time-in-range is 70%. These data were presented during the American Diabetes Association 82nd Scientific Sessions Conference on June 6, 2022 in New Orleans, Louisiana from 9:00 to 9:15 a.m. CDT as an oral abstract presentation, "Stem Cell-Derived, Fully Differentiated Islet Cells for Type 1 Diabetes". The presentation included data from both patients dosed in Part A of the study, designed to assess the safety profile of VX-880 at half the target dose. Patient 1 showed a blood glucose time-in-range increase from 40.1% at baseline to 99.9% at Day 270 and was insulin independent. Patient 2 showed a time-in-range increase from 35.9% at baseline to 51.9% at Day 150 with a 30% reduction in exogenous insulin use. VX-880 has been generally well tolerated in all patients dosed to date, with the majority of adverse events being mild or moderate. Additional Vertex presentations at ADA this year included an oral presentation, "Persistence of Impaired Awareness of Hypoglycemia, Severe Hypoglycemic Events and Suboptimal Glycemic Control Despite Advanced Diabetes Technologies", and poster, "Gaps Remain in Achieving Target T1D Glycemic Goals Despite Advanced Technologies". To date, three patients have been dosed in the Phase 1/2 study with VX-880. Two patients received half the target dose of cells in Part A of the study. A third patient has received the full target dose in Part B of the study. Vertex is also pursuing additional programs in T1D, including one in which these same stem cell-derived islets are encapsulated in an immunoprotective device to be surgically implanted without the use of concomitant immunosuppression, and another program where cells are modified to produce hypoimmune stem cell-derived islets. IND-enabling studies for the encapsulated cells program are underway, and the company remains on track to submit an IND in 2022.

Vertex Pharmaceuticals (VRTX) and CRISPR Therapeutics (CRSP) announced new late-breaking clinical data accepted for oral presentation at the 2022 European Hematology Association, or EHA, Congress. Late-breaking abstract #LB2367 entitled "Efficacy and Safety of A Single Dose of CTX001 For Transfusion-Dependent undefinedeta-Thalassemia and Severe Sickle Cell Disease," will be an oral presentation on Sunday, June 12. The abstract from Vertex and CRISPR Therapeutics includes data on patients treated in CLIMB-111 and CLIMB-121 and followed in CLIMB-131 with CTX001, now known as exagamglogene autotemcel, or exa-cel. This abstract has been selected for the media briefing program and is therefore embargoed until Saturday, June 11. Vertex also announced three abstracts accepted for poster presentation at EHA.