On June 11, 2022 Genmab A/S (Nasdaq: GMAB) reported that primary results from the large B-cell lymphoma (LBCL) expansion cohort in the EPCORE NHL-1 phase 2 clinical trial evaluating subcutaneous epcoritamab (DuoBody-CD3xCD20), an investigational bispecific antibody (Press release, Genmab, JUN 11, 2022, View Source [SID1234615908]). In the study, treatment with epcoritamab demonstrated deep and durable responses with an overall response rate (ORR) of 63 percent and a complete response rate (CR) of 39 percent in patients who had previously received at least two prior lines of systemic anti-lymphoma therapy. Additionally, patients naïve to treatment with chimeric antigen receptor (CAR) T-cell therapy achieved 69 percent ORR and 42 percent CR and patients previously treated with CAR T achieved a 54 percent ORR and 34 percent CR. Data were presented in a late-breaking oral presentation as a part of the Presidential Symposium at the 27th Annual Meeting of the European Hematology Association (EHA) (Free EHA Whitepaper) (EHA2022) in Vienna, Austria (Abstract #LB2364).

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"Large B-cell lymphoma is a fast-growing, difficult to treat type of aggressive non-Hodgkin’s lymphoma. Some treatment approaches like chemotherapy and immunotherapy have been in place for decades and newer treatments like CAR T-cell therapies involve multiple steps before a patient can begin treatment, so there is still a need for additional treatment options," said Professor Catherine Thieblemont, Head of the Hemato-Oncology Department at Hôpital Saint-Louis, Paris, France. "The data presented today suggest that epcoritamab has the potential to provide patients living with relapsed/refractory LBCL an accessible, effective treatment with a safety profile that may fulfill an unmet need."

The study cohort, which included 157 relapsed/refractory LBCL patients, previously treated with a median of three lines of prior therapy, demonstrated an overall response rate (ORR) of 63 percent and a complete response rate (CR) of 39 percent. Baseline characteristics included 61 percent of patients who were refractory to primary treatment, 20 percent who had prior autologous stem cell transplantation (ASCT), and 39 percent who were treated with CAR T-cell therapy (75 percent of those refractory to CAR T). Patients enrolled in the study who were naïve to CAR T therapy achieved a 69 percent ORR and a 42 percent CR and patients who received prior CAR T-cell treatment achieved a 54 percent ORR and a 34 percent CR. After a median follow up of 10.7 months, the median duration of response (mDOR) was estimated to be 12 months, while the mDOR among patients achieving a CR was not reached, with 89 percent still in CR at nine months. Topline results from this study were previously announced in April 2022.

"These latest data are promising because they suggest that treatment with epcoritamab may benefit patients with this fast-growing, aggressive and difficult to treat type of non-Hodgkin’s lymphoma who are in need of new therapeutic advances," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We are encouraged by the potential of epcoritamab and look forward to continuing to advance our robust clinical development program with our partner, AbbVie."

The safety profile of epcoritamab was manageable and consistent with previous findings. The majority of treatment-emergent AEs (TEAEs) occurred during the first 12 weeks of treatment and resolved. The most common TEAEs of any grade (greater than or equal to 15 percent) included cytokine release syndrome (CRS) (49.7 percent), pyrexia (23.6 percent), fatigue (22.9 percent), neutropenia (21.7 percent), diarrhea (20.4 percent), injection site reaction (19.7%), nausea (19.7%), and anemia (17.8%). The most common Grade 3 or 4 treatment-emergent adverse events (greater than or equal to 5 percent) included neutropenia (14.6 percent), anemia (10.2 percent), neutrophil count decrease (6.4 percent), and thrombocytopenia (5.7 percent). The observed Grade 3 CRS was low (2.5 percent). No Grade 4/5 CRS was observed.

Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ broad oncology collaboration. The companies remain committed to evaluating epcoritamab as a monotherapy, and in combination, across lines of therapy for a variety of hematologic malignancies, including an ongoing phase 3, open-label, randomized trial evaluating epcoritamab as a monotherapy in patients with relapsed/refractory DLBCL (NCT: 04628494).

About Large B-cell Lymphoma (LBCL)
LBCL is a fast-growing type of non-Hodgkin’s lymphoma (NHL) – a cancer that develops in the lymphatic system – that affects B-cell lymphocytes, a type of white blood cell. There are an estimated 150,000 new LBCL cases each year globally. LBCL includes DLBCL, which is the most common type of NHL worldwide and accounts for approximately 31 percent of all NHL cases.1,2,3,4

About the EPCORE NHL-1 Trial
EPCORE NHL-1 an open-label, multi-center safety and preliminary efficacy trial of epcoritamab including a phase 1 first-in-human, dose escalation part; a phase 2 expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-NHL, including LBCL and DLBCL. The dose escalation findings, which determined the recommended phase 2 dose, were published in The Lancet in 2021. In the phase 2 expansion part, additional patients are treated with epcoritamab to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-NHLs who had limited therapeutic options.

The primary endpoint of the phase 2 expansion part was ORR as assessed by an IRC. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were evaluated as secondary efficacy endpoints.

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response towards target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B-cells and induces T cell mediated killing of CD20+ cells.5 Epcoritamab was developed with selective, silencing mutations that may limit systemic, non-specific activity. CD20 is expressed on B-cells and a clinically validated therapeutic target in many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.6,7 Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ broad oncology collaboration.

On June 11, 2022 Oxford Drug Design reported that it will be attending the 28th tRNA Conference, 12-16 June 2022 in Columbus, Ohio, USA (Press release, Oxford Drug Design, JUN 11, 2022, View Source [SID1234615907]). On 13 June at 4:45pm EST Paul will be participating in a Panel Discussion on "Emerging Opportunities in tRNA Therapeutics", which will showcase the emerging opportunities for translational science and entrepreneurism in tRNA-related therapeutics and biotechnology across multiple therapeutic areas and treatment modalities. This is an exciting area with untapped therapeutic potential in which Oxford Drug Design is taking a leading position.

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On June 11, 2022 Orphagen Pharmaceuticals, an early-stage biopharmaceutical company focused on developing and commercializing novel therapies for cancer and other serious diseases with significant unmet need, reported that additional data from its preclinical program to develop OR-449 for the treatment of adrenocortical cancer (ACC) was presented at the 104th Annual Meeting of the Endocrine Society (ENDO 2022) being held in Atlanta from June 11 to 14 (Press release, Orphagen, JUN 11, 2022, View Source [SID1234615906]). ACC is a rare endocrine malignancy frequently diagnosed at an advanced stage with very limited treatment options. OR-449 is in preclinical development for treatment of ACC with a first-in-human clinical trial targeted for early 2023.

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OR-449 is a potent, selective, and orally bioavailable small molecule antagonist to steroidogenic factor-1 (SF-1 or NR5A1), a nuclear receptor and a transcription factor essential for the growth and development of the adrenal gland. SF-1 was recently described as a candidate "master transcription factor" in adult ACC.1 ACC tumors often secrete a "malignant" but variable pattern of steroids not normally found in the circulation. The preclinical findings reported show, first, that a malignant steroid profile is also secreted from two separate patient-derived ACC xenografts maintained in immunocompromised mice. Second, the secreted steroids from SW1939, derived from a pediatric ACC, were markedly regulated by treatment with OR-449. Similar steroid regulation in response to OR-449 treatment could occur in the clinic, facilitating selection of a treatment dose for a Phase 2 clinical trial.

Paul Crowe, Ph.D., presenting author and Vice President of Drug Discovery at Orphagen, stated, "We are once again excited to share preclinical data for the efficacy of OR-449 in ACC, this time in a novel preclinical model, the pediatric ACC xenograft, SW1939, developed by Peter Houghton and colleagues at U. T. Health Sciences Center in San Antonio. Not only does OR-449 inhibit the growth of this patient-derived xenograft, but it also regulates the levels of circulating adrenocortical tumor-derived steroids and steroid precursors. Circulating steroid secretion may provide a clinically relevant pharmacodynamic biomarker for OR-449 target engagement in ACC patients."

Orphagen CEO, Scott Thacher, Ph.D., said, "This is a satisfying success story for Orphagen’s corporate strategy to find first-in-class small molecules for unexplored nuclear receptor targets with efficacy in translationally relevant animal models of disease. The biomarker findings are a secondary, but potentially highly valuable outcome of these preclinical studies. We’re grateful for the strong support we’ve received from leading clinical investigators in the ACC field during this preclinical work, and we look forward to working with them on clinical trials for OR-449. Our hope is to bring a new and valuable therapeutic option to ACC patients."

Click to VIEW POSTER

Poster Presentation Information

Title: Downstream Targets of the Steroidogenic Factor-1 (SF-1) Antagonist OR-449 in PDX Models of ACC

Presenter: Paul D Crowe, PhD

Co-Authors: Ray Fox, PhD, Haiyan Tao, PhD, Neil Raheja, PhD, Richard J. Auchus, MD, PhD, Peter Houghton, PhD, Scott Thacher, PhD

Poster Session: PSUN355

1 Corces et al., Science. 2018; 362(6413); Reddy et al., Sci Adv. 2021; 7(48).

On June 11, 2022 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) and CRISPR Therapeutics (Nasdaq: CRSP) reported that 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 (TDT) or severe sickle cell disease (SCD) and provided additional program updates (Press release, CRISPR Therapeutics, JUN 11, 2022, View Source [SID1234615905]).

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New Data for exa-cel from CLIMB Clinical Studies
The data presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 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 (HbF) and corresponding increases in mean total hemoglobin (Hb) with mean total Hb levels increasing to >11 g/dL by Month 3 and maintained thereafter.

All 31 patients with severe SCD characterized by recurrent vaso-occlusive crises (VOCs) (mean of 3.9 VOCs per year over the prior two years) 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 (as a proportion of total Hb) 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 (SAEs) considered related to exa-cel. As previously reported, one patient had three SAEs considered related to exa-cel, hemophagocytic lymphohistiocytosis (HLH), 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.

Additional details were presented during the EHA (Free EHA Whitepaper) media briefing and can be found in the published abstract and presentation.

Late-breaking abstract #LB2367 entitled "Efficacy and Safety of a Single Dose of CTX001 For Transfusion-Dependent Βeta-Thalassemia and Severe Sickle Cell Disease," will be an oral presentation on Sunday, June 12 at 09:45-11:15 CEST.

"These robust data from 75 patients, of which 33 have one year or more of follow-up after exa-cel infusion, further demonstrate the potential of this investigational therapy as a one-time functional cure for patients with transfusion-dependent beta thalassemia or severe sickle cell disease," said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex.

"By reactivating a naturally occurring developmental process, exa-cel restores fetal hemoglobin production and thereby can ameliorate the course of these diseases," said Haydar Frangoul, M.D., Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute, HCA Healthcare’s The Children’s Hospital at TriStar Centennial Medical Center. "The remarkable results based on this approach give me great optimism and confidence in the potential of this treatment for patients."

"I have seen first-hand the impact that this investigational therapy has had on patients in these clinical trials and continue to be impressed by the totality of the data," said Franco Locatelli, M.D., Ph.D., Professor of Pediatrics at the Sapienza University of Rome, Director of the Department of Pediatric Hematology and Oncology at Bambino Gesù Children’s Hospital. "Given the urgency for highly effective and curative therapies for patients with hemoglobinopathies, I am excited to be part of the team working towards the goal of addressing this unmet need."

Exa-cel Study Updates
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 ≥9 g/dL without red blood cell (RBC) 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 ≥20% 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.

Additional Pediatric 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 (DMC) 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 (Free EHA Whitepaper) Congress.

Abstract #P1704 entitled "Projected Lifetime Economic Burden of Severe Sickle Cell Disease in the United States," presented via poster on Friday, June 10 at 16:30-17:45 CEST.
Abstract #P1703 entitled "Economic Burden of Transfusion-Dependent Beta-Thalassemia in the United States," presented via poster on Friday, June 10 at 16:30-17:45 CEST.
Abstract #P1482 entitled "Patients With Severe Sickle Cell Disease on Standard-of-Care Treatment Are Very Unlikely to Become VOC-Free for One Year: A Cohort Study of Medicaid Enrollees," presented via poster on Friday, June 10 at 16:30-17:45 CEST.
About exagamglogene autotemcel (exa-cel)
Exa‑cel, formerly known as CTX001, is an investigational, autologous, ex vivo CRISPR/Cas9 gene‑edited therapy that is being evaluated for patients with TDT or SCD characterized by recurrent VOCs, in which a patient’s own hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen‑carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. The elevation of HbF by exa‑cel has the potential to alleviate transfusion requirements for patients with TDT and reduce painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published in The New England Journal of Medicine in January of 2021.

Based on progress in this program to date, exa‑cel has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both TDT and SCD. Exa-cel has also been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA), for both TDT and SCD.

Among gene‑editing approaches being evaluated for TDT and SCD, exa‑cel is the furthest advanced in clinical development.

About CLIMB‑111 and CLIMB‑121
The ongoing Phase 1/2/3 open‑label trials, CLIMB‑111 and CLIMB‑121, are designed to assess the safety and efficacy of a single dose of exa‑cel in patients ages 12 to 35 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now closed for enrollment. Patients will be followed for approximately two years after exa‑cel infusion. Each patient will be asked to participate in CLIMB‑131, a long‑term follow‑up trial.

About CLIMB-131
This is a long‑term, open‑label trial to evaluate the safety and efficacy of exa‑cel in patients who received exa‑cel in CLIMB‑111, CLIMB‑121, CLIMB‑141 or CLIMB‑151. The trial is designed to follow participants for up to 15 years after exa‑cel infusion.

About CLIMB‑141 and CLIMB‑151
The ongoing Phase 3 open-label trials, CLIMB‑141 and CLIMB‑151, are designed to assess the safety and efficacy of a single dose of exa‑cel in patients ages 2 to 11 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now open for enrollment and currently enrolling patients ages 5 to 11 years of age 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.

About the Gene‑Editing Process in These Trials
Patients who enroll in these trials will have their own hematopoietic stem and progenitor cells collected from peripheral blood. The patient’s cells will be edited using the CRISPR/Cas9 technology. The edited cells, exa‑cel, will then be infused back into the patient as part of an autologous hematopoietic stem cell transplant (HSCT), a process which involves a patient being treated with myeloablative busulfan conditioning. Patients undergoing HSCT may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of exa‑cel. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of exa‑cel on multiple measures of disease and for safety.

About the Vertex‑CRISPR Collaboration
Vertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. Exa‑cel represents the first potential treatment to emerge from the joint research program. Under an amended collaboration agreement, Vertex now leads global development, manufacturing and commercialization of exa‑cel and splits program costs and profits worldwide 60/40 with CRISPR Therapeutics.

On June 11, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported that positive results from the Company’s ongoing Phase 1 COBALT-LYM trial evaluating the safety and efficacy of CTX130, its wholly-owned allogeneic CAR-T cell therapy targeting CD70 for the treatment of both solid tumors and certain hematologic malignancies (Press release, CRISPR Therapeutics, JUN 11, 2022, View Source [SID1234615903]).

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"We are very pleased with the preliminary results from our COBALT-LYM trial, which showed efficacy and safety that suggest that CTX130, the first allogeneic CAR-T directed against the novel target CD70, can produce deep responses in patients with relapsed or refractory T cell lymphomas," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. "Additionally, we may be able to further optimize the profile by continuing our consolidation dosing strategy. These data reinforce our belief that engineered cell therapies are the future in our fight against cancer and we are well-positioned to be leaders in this field."

"While overall survival in a subset of patients with T cell lymphoma has improved with front-line combination chemotherapy, relapsed or refractory patients continue to have very limited treatment options," said Swaminathan P. Iyer, M.D., Professor, Lead of the T Cell Lymphoma Program, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. "The data from the CTX130 trial demonstrate the potential of cell therapies as a new treatment modality for these patients. I am particularly encouraged by the response rates and safety data, which suggest that treatment with CTX130 could elicit clinically meaningful responses, including complete responses, in patients with difficult-to-treat T cell lymphomas."

COBALT-LYM Trial Overview
The Phase 1 COBALT-LYM trial is an open-label, multicenter clinical trial evaluating the safety and efficacy of CTX130 in adult patients with relapsed or refractory T or B cell malignancies. Dose escalation of CTX130 was performed in adult patients with relapsed or refractory T cell lymphoma, with at least 10% expression of CD70. Patients who received prior treatment with any CD70 targeting agents were not eligible.

Patients received three days of lymphodepleting chemotherapy, consisting of fludarabine at 30 mg/m2/day and cyclophosphamide at 500 mg/m2/day, followed by a single CTX130 infusion. Patients completed screening in as few as five days, and the median time from enrollment to the start of lymphodepleting chemotherapy was only three days. This timeline was possible because there is no need for leukapheresis or bridging chemotherapy, and CTX130 is available at the site before a patient is enrolled. Additionally, patients who showed clinical benefit from the first CTX130 infusion could be re-dosed following disease progression.

As of the April 26, 2022, data cutoff, 19 patients with T cell malignancies had been enrolled, of which 18 patients had received CTX130 with at least 28 days of follow-up and are included in the analysis. Prior to enrollment, all patients were heavily pre-treated, with a median of four systemic therapies. Additionally, all patients were refractory to their last line of therapy. Eight patients had peripheral T-cell lymphoma (PTCL) and 10 patients had cutaneous T-cell lymphoma (CTCL).

The primary endpoints include safety as measured by the incidence of dose limiting toxicities (DLTs) and overall response rate (ORR). Key secondary endpoints include progression free survival (PFS) and overall survival (OS).

Safety
CTX130 was well tolerated across all dose levels. The adverse events of interest for all evaluable patients are shown in the table below.

There were no cases of Graft versus Host Disease (GvHD); no dose limiting toxicities (DLTs); and no instances of tumor lysis syndrome (TLS).

All cases of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were Grade 1 or 2 per the American Society for Transplantation and Cellular Therapy (ASTCT) criteria and either required no specific intervention or resolved following standard CRS management. Neither the frequency nor severity of CRS has increased in patients who were re-dosed with CTX130.

There was a sudden death in one patient with William’s syndrome in the context of a lung infection, deemed unrelated to CTX130. There were no treatment related deaths in the trial. Overall, CTX130 has an emerging safety profile that is well tolerated.

Clinical Activity
Deep responses were seen with CTX130 in a significant fraction of patients at DL3 and above. Data are shown below for the 18 patients who received CTX130 and had at least 28 days of follow-up. Disease assessment was performed by investigator review according to the 2014 Lugano Response Criteria for PTCL or the International Society for Cutaneous Lymphoma Response Criteria (Olsen criteria) for CTCL, as appropriate.

Patients were heavily pre-treated with a median of four systemic therapies prior to enrollment in the study. None of the 18 patients had achieved a complete response (CR) in their previous line of therapy.

Median CD70 expression among the patients was 90%. Responses were observed across all levels of CD70 expression.

Clinically meaningful responses were observed with CTX130 with a higher percentage of patients responding at higher dose levels. At DL3 and above, ORR was 70% with 30% of patients achieving a CR. In addition, 90% of patients at DL3+ had clinical benefit defined as a stable disease or better response. These responses were largely consistent in both PTCL and CTCL with ORRs of 80% and 60%, respectively, at DL3+.

Broad activity and deep responses were seen in all disease compartments including lymph nodes, skin and blood in patients with CTCL following treatment with CTX130.
These preliminary data demonstrate that CTX130 has the potential to provide meaningful clinical benefit with a well-tolerated safety profile. Given the inherent difficulties and potential risks of manufacturing a CAR-T therapy from a patient’s own diseased T cells, allogeneic cellular therapy approaches for T cell lymphoma have greater potential to address the unmet need in this patient population.

CTX130 is currently being investigated in two ongoing Phase 1 clinical trials for the treatment of various subtypes of lymphoma (COBALT-LYM) or relapsed or refractory renal cell carcinoma (COBALT-RCC), respectively. Additional details on COBALT-LYM may be found at clinicaltrials.gov, using identifier: NCT04502446. In parallel, the Company continues to advance the rest of its immuno-oncology portfolio.

The Company plans to recap this data during the CRISPR Therapeutics Innovation Day, an event focused on early research and development, on June 21, 2022, at 2:00 pm ET.

Innovation Day Webcast
A live webcast of the event will be available on the "Events & Presentations" page in the Investors section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 30 days following the presentation. Please contact [email protected] for any questions regarding the event.

About CTX130
CTX130, a wholly-owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX130 is being developed for the treatment of both solid tumors, such as renal cell carcinoma, and T-cell and B-cell hematologic malignancies. CTX130 is being investigated in two ongoing independent Phase 1, single-arm, multi-center, open-label clinical trials that are designed to assess the safety and efficacy of several dose levels of CTX130 for the treatment of relapsed or refractory renal cell carcinoma and various subtypes of lymphoma, respectively. CTX130 for the treatment of T-cell lymphoma has received Orphan Drug Designation from the FDA.

About COBALT-LYM
The ongoing Phase 1 single-arm, multi-center, open label clinical trial, COBALT-LYM, is designed to assess the safety and efficacy of several dose levels of CTX130 for the treatment of relapsed or refractory T- or B-cell malignancies.

About COBALT-RCC
The ongoing Phase 1 single-arm, multi-center, open label clinical trial, COBALT-RCC, is designed to assess the safety and efficacy of several dose levels of CTX130 for the treatment of relapsed or refractory Renal Cell Carcinoma.