On June 11, 2021 Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX) and CRISPR Therapeutics (Nasdaq:CRSP) reported new data on 22 patients, with follow-up of at least 3 months, and ranging from 4 months to 26 months, treated with the investigational CRISPR/Cas9-based gene-editing therapy, CTX001, that show a consistent and sustained response to treatment (Press release, Vertex Pharmaceuticals, JUN 11, 2021, View Source [SID1234583849]). CTX001 is being investigated in two ongoing Phase 1/2 clinical trials as a potential one-time therapy for patients suffering from transfusion-dependent beta thalassemia (TDT) and severe sickle cell disease (SCD). In total, more than 40 patients have been dosed across both studies to date.

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All 15 patients with TDT, including six who have the beta zero/beta zero or other severe genotypes, were transfusion-free at last follow-up, and all seven patients with severe SCD were free of vaso-occlusive crises (VOCs) from CTX001 infusion through last follow-up. Five patients with TDT and two patients with SCD now have follow-up of greater than one year, demonstrating a stable and durable response to treatment. These data are available as e-posters beginning on June 11, 2021, at 09:00 CEST, and a partial presentation of these data were presented during the Joint EHA (Free EHA Whitepaper)-ASH Symposium on June 10, 2021 from 17:30-18:30 CEST. A summary of the results from the CLIMB-111 and CLIMB-121 Phase 1/2 clinical trials is provided below.

"The data presented today in 22 patients are impressive in both the consistency and durability of effect. These results add to the growing body of evidence that CTX001 may hold the promise for a one-time functional cure for sickle cell disease and beta thalassemia. We are working with urgency to complete enrollment and look forward to finalizing regulatory discussions and moving towards filing," said Reshma Kewalramani, M.D., Chief Executive Officer and President at Vertex.

"The continued progress and momentum of CTX001 validate the role that CRISPR gene-editing technology could have in the future of therapeutics," added Samarth Kulkarni, Ph.D., Chief Executive Officer at CRISPR Therapeutics. "We are excited about these results and look forward to additional longer-term data and to moving this investigational medicine forward for a larger population of patients with these two devastating diseases."

"As a physician caring for patients suffering from beta thalassemia, I have a high sense of urgency for novel and efficacious treatments," said Dr. Franco Locatelli, Professor of Pediatrics at the Sapienza University of Rome, Director of the Department of Pediatric Hematology and Oncology at Bambino Gesù Children’s Hospital. "These results suggest the potential for a durable benefit for patients with transfusion-dependent beta thalassemia."

"It is thrilling to work on a groundbreaking program like CTX001," said Dr. Stephan Grupp, Section Chief, Cellular Therapy and Transplant, Division of Oncology, Children’s Hospital of Philadelphia. "This approach uses CRISPR/Cas9 gene editing to enable the patient’s own cells to produce fetal hemoglobin, and to see results that demonstrate the potential for a treatment that may transform the lives of many patients is an exciting time for me and the team."

CLIMB-111 Trial in TDT: Updated Results
The 15 patients with TDT reported at EHA (Free EHA Whitepaper) are patients who had reached at least three months of follow-up after CTX001 dosing and therefore could be assessed for initial safety and efficacy. All 15 patients showed a similar pattern of response, with rapid and sustained increases in total hemoglobin, fetal hemoglobin and transfusion independence.

All 15 patients were transfusion independent with follow-up ranging from 4 to 26 months after CTX001 infusion and had clinically meaningful improvements in total hemoglobin from 8.9 to 16.9 g/dL and fetal hemoglobin from 67.3% to 99.6% at last visit.

Bone marrow allelic editing data collected from 10 patients with at least 6 months of follow-up, of which five patients had at least 12 months of follow-up and one patient had at least 24 months of follow-up, demonstrated a durable effect.

The safety data from all 15 patients were generally consistent with an autologous stem cell transplant and myeloablative conditioning. As previously reported, there were four serious adverse events (SAEs) considered related or possibly related to CTX001 reported in one patient: headache, hemophagocytic lymphohistiocytosis (HLH), acute respiratory distress syndrome and idiopathic pneumonia syndrome. All four SAEs occurred in the context of HLH and have resolved. The majority of non-serious adverse events were considered mild to moderate.

The presentations at EHA (Free EHA Whitepaper) and the data summarized in this press release cover all TDT patients dosed with CTX001 with three or more months of follow-up as of the data cut on March 30, 2021. In addition to the data presented above, a TDT patient, with less than three months of follow-up and therefore not included in the data cut, experienced an SAE; this SAE of cerebellar hemorrhage, which was considered related to busulfan conditioning, has resolved.

Enrollment and dosing are ongoing.

CLIMB-121 Trial in Severe SCD: Updated Results
The seven patients reported at EHA (Free EHA Whitepaper) are patients who had reached at least three months of follow-up after CTX001 dosing and therefore could be assessed for initial safety and efficacy. All seven patients showed a similar pattern of response, with rapid and sustained increases in total hemoglobin and fetal hemoglobin, as well as elimination of VOCs.

All seven patients remained VOC-free with follow-up ranging from five to 22 months after CTX001 infusion and had clinically meaningful improvements in total hemoglobin from 11 to 15.9 g/dL and fetal hemoglobin levels from 39.6% to 49.6% at last visit.

Bone marrow allelic editing data collected from four patients who have at least six months of follow-up, of which two had 12 months of follow-up, demonstrated a durable effect.

The safety data from all seven patients were generally consistent with an autologous stem cell transplant and myeloablative conditioning. There were no SAEs considered related to CTX001, and the majority of non-serious adverse events were considered mild to moderate.

Enrollment and dosing are ongoing.

About CTX001
CTX001 is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patient’s hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate or eliminate transfusion requirements for patients with TDT and reduce or eliminate painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published as a Brief Report in The New England Journal of Medicine in January of 2021.

Based on progress in this program to date, CTX001 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. CTX001 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 investigated/evaluated for TDT and SCD, CTX001 is the furthest advanced in clinical development.

About CLIMB-111
The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with TDT. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-121
The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with severe SCD. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-131
This is a long-term, open-label trial to evaluate the safety and efficacy of CTX001 in patients who received CTX001 in CLIMB-111 or CLIMB-121. The trial is designed to follow participants for up to 15 years after CTX001 infusion.

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, CTX001, will then be infused back into the patient as part of a stem cell transplant, a process which involves, among other things, a patient being treated with myeloablative busulfan conditioning. Patients undergoing stem cell transplants may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of CTX001. 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 CTX001 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. CTX001 represents the first potential treatment to emerge from the joint research program. Under a recently amended collaboration agreement, Vertex will lead global development, manufacturing and commercialization of CTX001 and split program costs and profits worldwide 60/40 with CRISPR Therapeutics.

On June 11, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported a poster presentation related to AUTO1 (obecabtagene autoleucel, obe-cel) in relapsed / refractory (r/r) indolent B cell lymphomas (IBCL) and included an update of duration of response in r/r adult Acute Lymphoblastic Leukemia (ALL) patients at the European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress 2021 (Press release, Autolus, JUN 11, 2021, View Source [SID1234583908]).

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"The stabilization of event-free survival at 50% between 12 months and 24 months of follow-up supports the curative potential of obe-cel as a standalone therapy for some adult ALL patients," said Dr. Christian Itin, chief executive officer of Autolus. "The early data we presented in indolent B cell non-Hodgkin lymphoma indicate a high level of clinical activity combined with a manageable safety profile and could represent a significant opportunity to expand the benefits of obe-cel treatment to a broader population of patients with B cell malignancies."

Title: Early safety and efficacy findings of AUTO1 (CAT19), a fast-off rate CD19 CAR, in Relapsed/Refractory Indolent B Cell Lymphomas

Presenter: Clare Roddie, MD, PhD, FRCPath, Consultant Haematologist and Honorary Senior Lecturer, Cancer Institute, University College London (UCL)

Session Date and Time: Friday, June 11, 2021 at 9.00 a.m. CEST

Relapsed / refractory (r/r) indolent B cell lymphomas
As of the data cut-off date of May 17, 2021, 13 patients in Cohort D with r/r IBCL had been enrolled in the study and product was successfully manufactured for 12 patients, with one patient’s cells ongoing in manufacture. As of the data cut-off date, 9 r/r IBCL patients had received AUTO1 infusion. Three patients were pending infusion (including the patient noted above) and one patient died prior to lymphodepletion due to a Covid-19 infection. Obe-cel was well tolerated and demonstrated a favorable safety profile in adult patients with r/r low grade B-cell lymphoma, despite high disease burden. All treated patients achieved a complete metabolic remission and had robust CAR T engraftment, expansion, and persistence.

Grade 1 cytokine release syndrome (CRS) was reported in 4 patients and Grade 2 CRS in 1 patient. No immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade was observed in the study. At a median follow-up of 6 months (range 4.0-8.1m), eight of nine patients were disease free at last follow-up with one patient who relapsed at month 6 but was rescued with radiotherapy. One patient died of a COVID-19 infection at month 5.6 whilst in complete metabolic remission.

Relapse / refractory adult Acute Lymphoblastic Leukemia
As of the data cut-off date of May 17, 2021, 20 patients in Cohort A with r/r ALL had received obe-cel. The therapy was well tolerated, with no patients experiencing Grade 3 or higher CRS. Three patients (15%), all of whom had high leukemia burden (>50% blasts), experienced Grade 3 ICANS that resolved swiftly with steroids.

Of the 20 patients evaluable for efficacy, 17 (85%) of patients achieved minimum residual disease (MRD)-negative complete remission (CR) at one month. Most notably, the durability of remissions is highly encouraging. Across all treated patients, event free survival (EFS) at twelve months and twenty-four months is 50.2% with median EFS not being reached.

Conference Call
Management will host a conference call and webcast today at 8:30 am ET/1:30 pm BST to discuss the data presented at EHA (Free EHA Whitepaper). To listen to the webcast and view the accompanying slide presentation, please go to the events section of Autolus’ website.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 3697562. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 3697562.

On June 11, 2021 The Executive Board of Epigenomics AG (Frankfurt Prime Standard: ECX, OTCQX: EPGNY; the "Company") reported that it has taken a decision in principle, with the approval of the Supervisory Board, to issue a subordinated mandatory convertible bond in an aggregate principal amount of up to EUR 18,150,000.00 (Press release, Epigenomics, JUN 11, 2021, View Source [SID1234583893]). This will be convertible into up to a total of 15,000,000 no-par value registered shares of the Company with a share of up to a total of EUR 15,000,000.00 in the share capital of the Company.

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The mandatory convertible bond will consist of up to 181,500 notes with a nominal amount of EUR 100.00 each, which will be offered for subscription by means of a rights offering initially to existing shareholders of Epigenomics AG. Shareholders will also be given the option of oversubscription. Furthermore, the Company plans to organize stock exchange trading of the subscription rights. The Company will shortly mandate an investment bank to accompany the issue and will start preparing a securities prospectus if legally necessary for the offering. The dates for the publication of a rights offering and the start of the subscription period will be published in due course.

In addition, today, Epigenomics AG has entered into a back-stop agreement with its shareholder Deutsche Balaton Aktiengesellschaft under which the latter has undertaken to acquire all notes in an aggregate principal amount of up to EUR 18,150,000.00 by exercising its subscription rights and by the acquisition of notes not subscribed via subscription rights and oversubscription rights. The obligation of Deutsche Balaton Aktiengesellschaft shall lapse in particular at the end of October 31, 2021, if the rights offering has not been published in the Federal Gazette by that date.

The notes will be non-interest-bearing (zero coupon) and have a term until 2027. In addition to conversion rights for the holders or creditors of the notes, they will also include a conversion obligation for all outstanding notes not yet converted at maturity.

Subject to any anti-dilution adjustments, the conversion price per share is EUR 1.21, i.e. each note with a nominal amount of EUR 100.00 will be convertible into 82 (eighty-two) no-par value registered shares representing EUR 1.00 per share of the Company’s share capital.

Epigenomics AG plans to use the proceeds from the convertible bond issue to finance its operations. Primarily, this is the completion of the development of the blood-based colorectal cancer screening test Epi proColon Next-Gen by conducting a clinical study in the U.S.A., which is required to obtain approval for the test by the U.S. Food and Drug Administration (FDA).

On June 11, 2021 Imago BioSciences, Inc. ("Imago"), a clinical stage biopharmaceutical company discovering new medicines for the treatment of myeloproliferative neoplasms (MPNs), reported updates on two Phase 2 clinical trials of bomedemstat, one in patients with essential thrombocythemia (ET) and, the second in patients with advanced myelofibrosis (MF) (Press release, Imago BioSciences, JUN 11, 2021, View Source [SID1234583909]). The data were presented in two e-poster presentations during the 26th European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress (EHA 2021), taking place June 9-17, 2021.

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Poster title: A Phase 2 Study of the LSD1 Inhibitor IMG-7289 (Bomedemstat) in Patients with Essential Thrombocythemia

The presented data show that bomedemstat was generally well-tolerated by patients with ET and demonstrated encouraging clinical activity as a monotherapy, showing symptomatic improvement in patients with significant MPN symptoms. Of the 12 patients dosed with bomedemstat for more than six weeks, 83% displayed substantial improvements in platelet count reduction, achieving platelets ≤ 400×109/L. Of the 10 patients entering the study with elevated white blood cell counts and evaluable at 12 weeks, 80% saw these counts fall within normal ranges. These improvements were achieved while maintaining stable hemoglobin levels. There were no dose limiting toxicities, no safety signals per Safety Advisory Board and one serious adverse event that was deemed unrelated.

"These encouraging data show that bomedemstat was well-tolerated and has the potential to bring meaningful clinical benefits for patients with essential thrombocythemia," said Wan-Jen Hong, M.D., chief medical officer of Imago BioSciences. "We are excited about these preliminary results from our lead asset, and look forward to completing enrollment of this study in order to lay the groundwork for a planned pivotal study in essential thrombocythemia."

Poster title: A Phase 2 Study of the LSD1 Inhibitor IMG-7289 (Bomedemstat) in Patients with Advanced Myelofibrosis

The presented data from an ongoing Phase 2 study indicated that bomedemstat as a monotherapy for patients with advanced MF offered a distinct clinical benefit profile, and was generally well-tolerated among participants. Of the 16 patients evaluable at 24 weeks, 94% showed improvements in total symptom scores (TSS), with a reduction of 50% or greater in almost a third of this subset. In an analysis of 34 patients evaluated for mutant allele frequencies (MAFs), MAFs decreased in 44% of patients and were stable in 47%, with no new mutations in up to 660 days of follow-up. Of the 18 patients evaluable for splenomegaly at 24 weeks, 89% had a reduction in spleen volume, with that of one patient decreasing by more than 35%. There were no dose limiting toxicities, no safety signals per Safety Advisory Board, and no progression to acute myeloid leukemia (AML).

"These updated clinical results reveal that bomedemstat continues to offer distinct clinical benefits for patients with advanced MF, showing overall improvement in total symptom scores, spleen volumes and anemia," said Wan-Jen Hong, M.D., chief medical officer of Imago BioSciences. "The study is now fully enrolled, so we look forward to sharing our cumulative data as we continue to advance this investigational program for patients who have few therapeutic alternatives."

Poster presentations are available on the EHA (Free EHA Whitepaper) Virtual Congress platform. The posters will also be available on the Imago website here.

On June 12, 2021 Daiichi Sankyo Company reported that it has received conditional and time-limited approval from the Japan Ministry of Health, Labour and Welfare (MHLW) for Delytact (teserpaturev/G47?), an oncolytic virus, for the treatment of patients with malignant glioma (Press release, Daiichi Sankyo, JUN 11, 2021, View Source [SID1234594392]).

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Delytact previously received SAKIGAKE Designation and Orphan Drug Designation from the MHLW for this indication and is now the first oncolytic virus to be approved in any region of the world for treatment of malignant glioma or any type of primary brain cancer. Daiichi Sankyo has been collaboratively developing Delytact with Dr. Tomoki Todo of the Institute of Medical Science, The University of Tokyo, and is the Marketing Authorization Holder of Delytact in Japan.

The approval of Delytact in Japan is based on results of a single-arm phase 2 clinical trial evaluating Delytact in patients with residual or recurrent glioblastoma, the most common and aggressive form of malignant glioma.1 The trial met its primary endpoint for one-year survival rate in an interim analysis. Results of the study will be submitted for publication by Dr. Todo.

"With the approval of Delytact in Japan we can now offer the first-ever oncolytic virustherapy option to patients with glioblastoma and other malignant gliomas that are not controlled with currently available treatments," said Wataru Takasaki, PhD, Executive Officer, Head of R&D Division in Japan, Daiichi Sankyo. "Delytact is the fourth oncology medicine to be approved in Japan for Daiichi Sankyo over the past two years and we are grateful for the opportunity to collaborate with Dr. Todo to deliver this truly innovative treatment modality to patients and physiciansin Japan."

Glioma, which originatesin glial cells in brain tissue, represents almost 80 percent of all malignant primary brain tumors. Glioma is classified from grade I to IV based on the level of malignancy.

The phase 2 open-label, single-arm, non-randomized, single-centerstudy conducted by Dr. Todo of the Institute of Medical Science, The University of Tokyo, evaluated the safety and efficacy of G47? (Delytact) in adult patients with glioblastoma who had been treated with radiotherapy and temozolomide chemotherapy and had one residual tumor or one recurrent lesion after the initial treatment.

The primary endpoint of the trial is one-year survival rate after initiation of Delytact therapy, analyzed using historical control. Secondary endpoints include progression-free survival, overall survival and overall response rate.

Delytact (teserpaturev/G47?) is a genetically engineered oncolytic herpes simplex virus type 1 (HSV-1) developed by Dr. Todo and his colleagues. Delytact has triple mutation within the viral genome that cause augmented and selective replication in cancer cells and enhanced induction of antitumor immune response while retaining high safety features. Delytact is currently the first third generation oncolytic HSV-1 to be evaluated in humans.

Delytact has received conditional and time-limited approval in Japan for the treatment of patients with malignant gliomas based on the phase 2 study results. Continued approval for this indication may be contingent upon verification and description of clinical benefit and safety in a post-market comparative clinical study. Delytact is not approved for any use outside of Japan.