On July 27, 2020 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the second quarter ended June 30, 2020 (Press release, CRISPR Therapeutics, JUL 27, 2020, View Source [SID1234562456]).

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"We continue to make substantial progress driving our multiple, ongoing clinical development programs. Enrollment in our immuno-oncology trials is ongoing, and we’ve re-initiated dosing in our CTX001 trials," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. "Further, we expect to report data from our CTX001 program targeting hemoglobinopathies and our CTX110 program later this year. Despite the challenges posed by COVID-19, we continue to execute on our programs and remain focused on our commitment to patients and their families."

Recent Highlights and Outlook

Beta Thalassemia and Sickle Cell Disease

CRISPR Therapeutics and its partner Vertex provided new clinical data at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress from the two ongoing Phase 1/2 studies of the investigational CRISPR/Cas9 gene-editing therapy CTX001 in patients with transfusion-dependent beta thalassemia (TDT) and in patients with severe sickle cell disease (SCD). Data from two TDT patients demonstrated clinical proof-of-concept for CTX001 in this disease, and longer duration data from one SCD patient showed durable effects on fetal hemoglobin (HbF) levels and the patient was free of vaso-occlusive crises. Screening, enrollment and mobilization in these studies are ongoing; conditioning and dosing have been resumed following temporary COVID-19-related pauses in both studies. CRISPR Therapeutics and Vertex expect to report data from additional patients in the second half of 2020.

In May, CRISPR Therapeutics and its partner Vertex announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to CTX001, an investigational, autologous, gene-edited hematopoietic stem cell therapy, for the treatment of TDT and SCD. In addition to RMAT designation, CTX001 has received Orphan Drug Designation from the U.S. FDA for TDT and SCD and from the European Commission for TDT and SCD. CTX001 also has Fast Track Designation from the U.S. FDA for both TDT and SCD.

Immuno-Oncology

Patient dosing continues in a clinical trial to assess the safety and efficacy of CTX110, CRISPR Therapeutics’ wholly-owned allogeneic CAR-T cell therapy targeting relapsed or refractory CD19+ B-cell malignancies. The Company expects to report top-line data for CTX110 at the end of 2020.

Patient dosing continues in a clinical trial to assess the safety and efficacy of CTX120, CRISPR Therapeutics’ wholly-owned allogeneic CAR-T cell therapy targeting BCMA for the treatment of relapsed or refractory multiple myeloma.

Two independent clinical trials assessing the safety and efficacy of CTX130, CRISPR Therapeutics’ wholly-owned allogeneic CAR-T cell therapy targeting CD70 for the treatment of both solid tumors and certain hematologic malignancies, are open for enrollment.

Other Corporate Matters

In June, CRISPR Therapeutics announced the pricing of an underwritten public offering of 6,428,572 common shares at a public offering price of $70.00 per share, plus the exercise in full of the underwriters’ option to purchase 964,285 additional common shares. Gross proceeds from the offering (including the exercise of the underwriters’ option), before deducting underwriting discounts and commissions and other offering expenses, were $517.5 million. The common stock offering and the option to purchase additional shares closed in July 2020.

CRISPR Therapeutics reported a research agreement with UHN, Canada’s largest research hospital, affiliated with the University of Toronto, and a member of the Toronto Academic Health Science Network. Through UHN’s McEwen Stem Cell Institute, the aim of the collaboration is to combine CRISPR Therapeutics’ gene editing technology with UHN’s methods for differentiating stem cells into hepatocytes at high yield and purity, with the goal of developing regenerative medicine cell therapies for a number of different diseases. The agreement provides CRISPR Therapeutics an option to commercialize the technology.

In June, CRISPR Therapeutics presented four posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II. The posters addressed the potential of CRISPR-modified CAR-T cells as follows: an assessment of CRISPR-modified CAR-T cells in patients with non-small cell lung cancer; functionality in vivo and in vitro of allogeneic CAR-T cell products containing multiple CRISPR/Cas9 gene edits; assessment of allogeneic anti-PTK7 CAR-T cells for the treatment of solid tumors; and the potential of CRISPR/Cas9-generated anti-CD70 allogeneic CAR-T cells to target T cell lymphomas.

CRISPR Therapeutics reported it entered into a lease agreement with Breakthrough Properties for a new location in Boston, Massachusetts. The new facility will consolidate CRISPR’s various office and laboratory locations in the greater Boston area into a single location and support the Company’s anticipated future growth for five to seven years from the date of occupancy, which is expected in 2022.

In June, CRISPR Therapeutics announced that it is building a new cell therapy manufacturing facility in Framingham, Massachusetts, for clinical and commercial production of the Company’s investigational cell therapy product candidates. The facility is being designed to provide GMP manufacturing according to FDA and European Medicines Agency (EMA) regulations and guidelines to support clinical supply and commercial product upon potential regulatory approval.
Second Quarter 2020 Financial Results

Cash Position: Cash and cash equivalents as of June 30, 2020 were $945.1 million compared to $889.7 million as of March 31, 2020, an increase of $55.4 million. The increase in cash was primarily driven by financing activities during the quarter of $89.5 million and the $25.0 million milestone received from Vertex in April. The increase was offset by cash used in operating activities during the quarter of $54.3 million (exclusive of the $25.0 million milestone received by Vertex in April) to support spending on the Company’s clinical and pre-clinical programs, as well as payroll and payroll-related expenses to support growth. After including the $484.8 million in net proceeds from our underwritten public offering completed in July, pro forma cash exceeds $1.4 billion.

Revenue: Total collaboration revenue was less than $0.1 million for the second quarter of 2020 compared to $0.3 million for second quarter of 2019. Collaboration revenue primarily consisted of charges to partners for research activities.

R&D Expenses: R&D expenses were $59.4 million for the second quarter of 2020 compared to $39.5 million for the second quarter of 2019. The increase in expenses was driven by increased headcount and development activities supporting the advancement of the hemoglobinopathies program and wholly-owned immuno-oncology programs.

G&A Expenses: General and administrative expenses were $21.4 million for the second quarter of 2020 compared to $15.8 million for the second quarter of 2019. The increase in general and administrative expenses for the year was driven by headcount-related expense and higher facilities cost.

Net Loss: Net loss was $79.7 million for the second quarter of 2020 compared to net loss of $53.7 million for the second quarter of 2019.
About CTX001
CTX001 is an investigational ex vivo CRISPR gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD in which a patient’s hematopoietic stem cells are engineered 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 and is then replaced by the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for TDT patients and painful and debilitating sickle crises for SCD patients.

CTX001 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and Vertex.

About CTX110
CTX110 is a healthy donor-derived gene-edited allogeneic CAR-T therapy targeting cluster differentiation 19, or CD19, for the treatment of CD19+ malignancies. A wholly-owned asset of CRISPR Therapeutics, CTX110 is being investigated in a clinical trial designed to assess the safety and efficacy of CTX110 for the treatment of relapsed or refractory B-cell malignancies. The multi-center, open-label clinical trial is designed to enroll up to 131 patients and investigate several dose levels of CTX110.

About CTX120
CTX120 is a healthy donor-derived gene-edited allogeneic CAR-T therapy targeting B-cell maturation antigen, or BCMA. A wholly-owned asset of CRISPR Therapeutics, CTX120 is being investigated in a clinical trial designed to assess the safety and efficacy of CTX120 for the treatment of relapsed or refractory multiple myeloma. The multi-center, open-label clinical trial is designed to enroll up to 88 patients and investigate several dose levels of CTX120.

About CTX130
CTX130 is a healthy donor-derived gene-edited allogeneic CAR-T 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. A wholly-owned asset of CRISPR Therapeutics, CTX130 is being investigated in two independent clinical trials that are designed to assess the safety and efficacy of CTX130 for the treatment of relapsed or refractory renal cell carcinoma and various subtypes of lymphoma, respectively. The multi-center, open-label clinical trial investigating CTX130 for the treatment of relapsed or refractory renal cell carcinoma is designed to enroll approximately 95 patients and investigate several dose levels of CTX130. The multi-center, open-label clinical trial investigating CTX130 for the treatment of various lymphomas is designed to enroll approximately 46 patients and investigate several dose levels of CTX130.

On July 27, 2020 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a late-stage clinical biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer,reported the acceptance of five oral presentations at the International Society of Pediatric Oncology ("SIOP") Virtual Annual Congress held October 14 through October 17, 2020 in Ottawa, Canada (Press release, Y-mAbs Therapeutics, JUL 27, 2020, View Source [SID1234562454]). The abstracts are publicly available online at View Source

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Naxitamab

The abstracts include the following presentations of naxitamab, one of the Company’s lead product candidates, which is currently being evaluated for the treatment of pediatric patients with relapsed or refractory high-risk neuroblastoma, osteosarcoma and other GD2-positive tumors:

"High-dose naxitamab (humanized-3F8) plus stepped-up dosing of granulocyte-macrophage colony-stimulating factor (GM-CSF) for resistant osteomedullary neuroblastoma: major responses and outpatient treatment in a Phase II trial," submitted by MSK in New York

"Naxitamab-based chemoimmunotherapy for resistant high-risk neuroblastoma: preliminary results of HITS treatment," submitted by SJD Barcelona Children’s Hospital in Barcelona, Spain

"Telemedicine blood pressure monitoring after anti-GD2 monoclonal antibody immunotherapy during the COVID-19 pandemic," submitted by MSK in New York
Naxitamab has been accepted for priority review by the U.S. Food and Drug Administration ("FDA") for the treatment of patients with relapsed/refractory high-risk neuroblastoma. The FDA set an action date of November 30, 2020, under the Prescription Drug User Fee Act ("PDUFA").

Omburtamab

The abstracts also include the following presentation of omburtamab, the Company’s other lead product candidate, which is currently being evaluated for the treatment of patients with CNS/Leptomeningeal metastasis from neuroblastoma, diffuse intrinsic pontine glioma ("DIPG"), and desmoplastic small round cell tumors ("DSRCT"):

"Intracerebroventricular radioimmunotherapy using 131I-omburtamab for neuroblastoma central nervous system/leptomeningeal metastases, interim results from multi-center trial 101," submitted by Memorial Sloan Kettering Cancer Center ("MSK") in New York
During June 2020, we initiated the submission of the Biologics License Application ("BLA") for omburtamab under the FDA’s Rolling Review process and completion of the BLA submission is currently expected to take place over the next few weeks.

GD2-GD3 Vaccine

The abstracts also include the following presentation of the GD2-GD3 Vaccine, the Company’s vaccine candidate, which is currently being evaluated for high-risk neuroblastoma patients in remission:

"Favorable toxicity profile of bivalent GD2/GD3 neuroblastoma vaccine," submitted by MSK in New York

On July 27, 2020 CARISMA Therapeutics Inc., a biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for the Company’s lead product candidate, CT-0508, an anti-human epidermal growth factor receptor 2 (HER2) targeted chimeric antigen receptor macrophage (CAR-M) (Press release, Carisma Therapeutics, JUL 27, 2020, View Source [SID1234562419]). Under this IND, CARISMA intends to initiate its Phase 1, first-in-human, multi-center study in patients with recurrent or metastatic HER2 overexpressing solid tumors after failure of approved HER2 targeted agents.

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"This will be the first time that an engineered macrophage has progressed successfully to the in-patient study phase and represents a new chapter for CARISMA: advancing from a preclinical discovery-stage company to a clinical development stage company," said Steven Kelly, President and Chief Executive Officer. "The clearance of our IND application for CT-0508 is a ground-breaking milestone in the field of cell-based cancer immunotherapy."

Historically, cell therapies have encountered key challenges treating solid tumors, including limited trafficking to the tumor site, an immunosuppressive tumor microenvironment, and the heterogeneous expression of tumor-associated antigens, but CARISMA’s preclinical findings suggest that CAR-M therapy could overcome these challenges.

"Our preclinical findings indicate that CAR-M have the ability to mount a broad immune response against cancers, and the acceptance of the CT-0508 IND brings this technology to patients with incurable solid tumors," said Michael Klichinsky, PharmD, PhD, co-inventor of the CAR-M technology, Scientific Co-founder, and Vice President of Discovery at CARISMA Therapeutics.

CARISMA Scientific Co-founder and Assistant Professor of Hematology-Oncology in Penn’s Abramson Cancer Center, Saar Gill, MD, PhD, added, "I’m incredibly pleased and excited to see the technology that was originally developed in my lab progress to the clinic. Getting a chance to translate your preclinical research and evaluate its potential impact for patients is the reason why I do this type of work."

The planned clinical trial will be conducted at two trial sites—University of Pennsylvania in Philadelphia, Pennsylvania, and University of North Carolina in Chapel Hill, North Carolina—and will enroll patients with different types of recurrent or metastatic cancers with HER2 overexpressing solid tumors.

"HER2 is overexpressed not only in breast and gastroesophageal cancers, but in a wide variety of epithelial origin solid tumors, such as non-small cell lung, colorectal, bladder, and pancreatic cancers," said Debora Barton, MD, Chief Medical Officer at CARISMA Therapeutics. "There is an important unmet medical need that remains to be addressed and we aim to achieve that during this clinical trial."

Corporate Developments

CARISMA also announced today the expansion of its Board of Directors to include Briggs W. Morrison, MD, as well as additions to the Scientific Advisory Board, Nina Bhardwaj, MD, PhD, and Prasad S. Adusumilli, MD.

"CARISMA is at an exciting juncture," said Mike Heffernan, Chairman of the Board of Directors. "Evolving from a preclinical stage company, having demonstrated reduced tumor burden and significantly improved overall survival with our CAR-M technology in humanized mouse models, to quickly approaching the in-clinic study of this first-of-its-kind therapy. We are eager to have Drs. Morrison, Bhardwaj and Adusumilli’s counsel as CARISMA embarks on this new chapter."

The CARISMA Board of Directors welcomes Dr. Briggs Morrison, who brings with him over 25 years of pharmaceutical, global regulatory and business development leadership experience. Joining the Scientific Advisory Board are Drs. Nina Bhardwaj and Prasad S. Adusumilli. Dr. Bhardwaj brings extensive immunology experience: she is currently the Director of Immunotherapy, Medical Director of the Vaccine and Cell Therapy Laboratory, and Co-Director of the Cancer Immunology Program at The Tisch Cancer Institute and holds the Ward Coleman Chair in Cancer Research. She has made influential contributions to human dendritic cell biology, specifically regarding isolation, biology, antigen presenting function and use as vaccine adjuvants in humans. Dr. Adusumilli, Deputy Chief of Thoracic Service at Memorial Sloan Kettering Cancer Center, brings his extensive experience with the investigation of the tumor immune microenvironment and the development of CAR T-cell-mediated immunotherapies.

On July 27, 2020 Agendia, Inc., a world leader in precision oncology for breast cancer, reported the publication of MINDACT trial data in the July 27 issue of Communications Biology, a Nature Publishers Journal (Press release, Agendia, JUL 27, 2020, View Source [SID1234562418]). In the largest data set seen to date, the study yielded a full transcriptome array for each tumor and demonstrated the successful removal of technical variation in gene expression profiles while retaining expected biological signals. The resulting dataset could serve as an invaluable tool to discover or test gene expression signatures in the Company’s quest to better elucidate the complexities of breast cancer.

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The paper, entitled, "Controlling technical variation amongst 6693 patient microarrays of the randomized MINDACT trial," is available online here.

"As part of our mission to bring patients and their doctors the data they need to make treatment decisions, we continue to conduct a number of studies and push research within our existing trials to ensure that our diagnostic tests, MammaPrint and BluePrint, offer reliable and actionable results," said Annuska Glas, PhD, Vice President of Research and Development at Agendia. "This is a major research and development milestone, achieved over 13 years, that will be used in future studies to help patients and physicians better understand breast cancer."

Gene expression data obtained in large studies are promising but in general are prone to technical variation, and removal of these variations is essential to avoid inaccurate conclusions. The publication provides a robust resource how for ensuring that initial variation affecting the full transcriptome expression data of a large dataset can be adjusted by removing over-time technical variations without losing biological signals for future analysis purposes.

The paper concluded that the analysis pipeline for this unprecedented achievement and sample size is entirely reproducible, and both adjusted and unadjusted breast cancer data sets are available and ready-to-use for translational research.

"We are happy to make this data and our process accessible for the community working to uncover every complexity of breast cancer," said Laura van’t Veer, PhD, Chief Research Officer and Co-Founder of Agendia.

The multi-faceted, real-world data library being built for the MINDACT trial underscores Agendia’s commitment to both long-term and immediately actionable research and dedication to consistently pushing the boundaries of previous findings to improve patient outcomes.

About the MINDACT Trial

MammaPrint, the 70-gene risk of recurrence assay for patients with early-stage breast cancer, is supported by level 1A clinical evidence from MINDACT, a landmark trial sponsored by the EORTC (EORTC-10041/BIG3-04). The study found that clinically high-risk patients with a MammaPrint Low Risk result could safely de-escalate treatment and forgo chemotherapy. Long-term follow-up data from MINDACT, presented at the 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), confirmed and built upon the findings published in the New England Journal of Medicine in 2016.

The MINDACT trial enrolled 6,693 breast cancer patients. At the five-year follow-up mark, the trial showed that tumor analysis and reclassification by the MammaPrint 70-gene expression signature enabled a 46 percent reduction in the use of chemotherapy for clinically high-risk patients that were reclassified by the genetic assay to be genomically Low Risk. Nine-year follow-up data will be published in depth later this year, and confirm MINDACT as a positive de-escalation study for chemotherapy and continues to demonstrate MammaPrint’s clinical utility when determining a breast cancer patient’s need for chemotherapy.

On July 27, 2020 Foresee Pharmaceuticals Co., Ltd. (6576.TWO) ("Foresee"), reported that it has submitted to the U.S. Food and Drug Administration a 505(b)(2) New Drug Application for Camcevi 42mg (FP-001 LMIS 50mg), a ready-to-use 6-month depot formulation of leuprolide mesylate (Press release, Foresee Pharmaceuticals, JUL 27, 2020, View Source [SID1234562417]). The application seeks approval for the use of this product for the palliative treatment of advanced prostate cancer.

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This NDA submission is supported by a previously communicated successful Phase 3 study in 137 Advanced Prostate Carcinoma patients, where treatment with LMIS 50 mg injection every 6 months was demonstrated to be effective, safe and well tolerated.

"In the NDA submission in 2019, FDA suggested that additional device design verification data on the combination product be provided. Since then, with tireless efforts and commitment from the Foresee team and collaborators, as well as continued support of our investors, we have undertaken diligent preparation for the requested information," said Dr. Ben Chien, Founder and Chairman of Foresee. "We are confident in the resubmission of the NDA."

"Next step for the FP-001 franchise will be to establish a strong commercial partnership in the US and to prepare for the NDA submission of the 3-month depot of Camcevi. We look forward to the successful launch of the FP-001 franchise, providing patients with its differentiated ready-to-use profile." said Dr. Ben Chien.