1stOncology™: Cancer Intelligence Service – Page 14624 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

G1 Therapeutics Announces Positive Feedback from Trilaciclib End-of-Phase 2
Meeting with FDA; Expects to File NDA in 2020

On April 29, 2019 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, reported a regulatory update on trilaciclib, a first-in-class myelopreservation agent designed to protect the bone marrow from damage by chemotherapy and improve patient outcomes (Press release, G1 Therapeutics, APR 29, 2019, View Source [SID1234535553]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

Based on written feedback from its end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) and discussions with European regulatory authorities, the company plans to submit marketing applications in the U.S. and Europe for trilaciclib for myelopreservation in small cell lung cancer (SCLC). These submissions will be based on currently available data from three randomized, double-blind, placebo-controlled SCLC clinical trials, as well as safety data collected across all completed and ongoing clinical trials.

"We are pleased with the feedback from our recent meetings with regulatory authorities. We look forward to continuing a collaborative dialogue regarding the marketing applications, as well as discussing further clinical development of trilaciclib," said Raj Malik, M.D., Chief Medical Officer. "We believe trilaciclib represents an important advance in the care of SCLC patients. We will also move forward with a robust development program to evaluate trilaciclib in multiple tumor types and chemotherapy regimens."

G1 will request a pre-New Drug Application (NDA) meeting with the FDA and anticipates it will be scheduled later this year. The company will provide further details regarding the NDA submission and timeline following that meeting. The company plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) subsequent to an NDA filing.

Chemotherapy is an effective and important weapon against cancer. However, chemotherapy does not differentiate between healthy cells and cancer cells and kills both, including important stem cells in the bone marrow that produce white blood cells, red blood cells and platelets. This chemotherapy-induced bone marrow damage is known as myelosuppression. When white blood cells, red blood cells and platelets become depleted, chemotherapy patients are at increased risk of infection, experience anemia and fatigue, and are at increased risk of bleeding. Myelosuppression often requires the administration of rescue interventions such as growth factors and blood or platelet transfusions, and may also result in chemotherapy dose delays and reductions.

"In clinical trials, trilaciclib demonstrated the ability to protect bone marrow from chemotherapy damage and meaningfully reduced the need for supportive care interventions, such as G-CSF and transfusions," said Jared Weiss, M.D., Associate Professor, University of North Carolina Lineberger Comprehensive Cancer Center, and trilaciclib clinical trial investigator. "By providing a proactive approach to reduce myelosuppression, trilaciclib improves the patient experience during chemotherapy treatment, reducing side effects and the need for associated interventions commonly given to treat them."

About Trilaciclib

Trilaciclib is a first-in-class myelopreservation agent designed to protect the bone marrow from damage by chemotherapy and improve patient outcomes. Trilaciclib is being evaluated in four randomized Phase 2 clinical trials; G1 reported positive results from all these trials in 2018.

Eagle Pharmaceuticals to Discuss First Quarter 2019 Financial Results on May 7, 2019

On April 29, 2019 Eagle Pharmaceuticals, Inc. ("Eagle" or the "Company") (Nasdaq: EGRX) reported that the Company will release its 2019 first quarter financial results on Tuesday, May 7, 2019, before the market opens (Press release, Eagle Pharmaceuticals, APR 29, 2019, View Source [SID1234535549]).

Scott Tarriff, Chief Executive Officer, and Pete Meyers, Chief Financial Officer, will host a conference call to discuss the results as follows:

Date Tuesday, May 7, 2019
Time
8:30 a.m. EDT

Toll free (U.S.) 877-876-9176
International 785-424-1670
Webcast (live and replay)
www.eagleus.com, under the "Investor Relations" section

A replay of the conference call will be available for one week after the call’s completion by dialing 800-839-5493 (US) or 402-220-2552 (International) and entering conference call ID EGRXQ119. The webcast will be archived for 30 days at the aforementioned URL.

Intellia Therapeutics Presents New In Vivo and Engineered Cell Therapy Data at the 22nd Annual Meeting of the American Society of Gene and Cell Therapy

On April 29, 2019 Intellia Therapeutics, Inc. (NASDAQ:NTLA), reported that it will present new data, including the first demonstration of targeted gene insertion with CRISPR/Cas9 in the liver of non-human primates (NHPs), at the 22nd Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper), taking place April 29-May 2, 2019, in Washington, D.C (Press release, Intellia Therapeutics, APR 29, 2019, View Source [SID1234535545]). Researchers also will present today new in vitro data from Intellia’s lead engineered cell therapy program in acute myeloid leukemia (AML). Later this week at the 2019 ASGCT (Free ASGCT Whitepaper) meeting, Intellia will present new data from its primary hyperoxaluria (PH1) program.

"The data we are presenting at ASGCT (Free ASGCT Whitepaper) reflects our rapid progress with Intellia’s modular CRISPR/Cas9 platform across a variety of in vivo and engineered cell therapeutic applications," said Intellia President and Chief Executive Officer John Leonard, M.D. "Today’s presentation of our most recent targeted gene insertion data depicts Intellia’s second successful demonstration of CRISPR-mediated gene editing in non-human primates, both in collaboration with Regeneron Pharmaceuticals, Inc. The first was through gene knockout in our transthyretin amyloidosis program and, now, we have used our targeted insertion approach with Factor 9 as a model gene. We also continue to make strides with our collaborators at IRCCS Ospedale San Raffaele toward developing engineered cell therapies for a variety of intractable cancers, such as acute myeloid leukemia."

Intellia’s First Demonstration of Targeted Gene Insertion in NHPs

In a follow-up to Intellia’s presentation at the 2018 European Society of Gene and Cell Therapy (ESGCT) meeting of the first robust demonstration of CRISPR-mediated insertion of transgenes in the liver of mice using Factor 9 (F9) as a model gene, the company will present at ASGCT (Free ASGCT Whitepaper) an advancement of its modular hybrid delivery system, which combines Intellia’s lipid nanoparticle (LNP) platform with an adeno-associated virus (AAV). F9 is a gene that encodes FIX, a blood-clotting protein that is missing or defective in hemophilia B patients.

In a collaboration between Intellia and Regeneron, researchers delivered F9 DNA via a proprietary bi-directional insertion template to demonstrate targeted gene insertion in NHPs, resulting in circulating human FIX protein levels within the normal range of human FIX protein levels (3-5 μg/mL; source: Amiral et al., Clin. Chem., 1984). Researchers observed circulating human FIX protein levels of ~3-4 μg/mL at day 14 after a single dose in an ongoing study, with levels sustained through 28 days (~3-5 μg/mL).

Today, researchers additionally will share updated results from an ongoing durability study, first reported in October, that the circulating supratherapeutic human FIX protein levels achieved in mice with Intellia’s hybrid LNP-AAV delivery system have remained stable through 10 months of observation. Further, researchers will show that they can regulate FIX protein levels in mice by varying LNP doses, AAV doses or insertion site.

Today’s presentation, titled "CRISPR/Cas9-Mediated Targeted Insertion of Human F9 Achieves Therapeutic Circulating Protein Levels in Mice and Non-Human Primates," will be made by Hon-Ren Huang, associate director, Vector Biology, Intellia. This presentation will be accessible through the Events and Presentations page of the Investor Relations section of Intellia’s website at www.intelliatx.com.

Data Update from Intellia’s Acute Myeloid Leukemia Program

Intellia and its research collaborator, IRCCS Ospedale San Raffaele, will provide an update on the company’s lead engineered cell therapy program in AML. Researchers will present new in vitro data showing that CRISPR/Cas9 editing resulted in >98% knockout of the endogenous T cell receptor (TCR), while achieving transfer of various Wilms’ Tumor 1 (WT1)-specific TCRs into >95% of isolated T cells. Researchers generated and tested a library of TCRs with different epitope specificities and human leukocyte antigen (HLA) restrictions, building on the data reported at the 2018 ESGCT meeting. Several lead TCRs restricted to the HLA-A*02:01 allele, a frequently expressed allele in the western hemisphere, show the desired T cell characteristics, including high affinity, epitope specificity and killing of a panel of primary leukemic blast cells that expressed the WT1 antigen.

Intellia and OSR are collaborating to develop best-in-class CRISPR-edited T cells directed to a specific epitope of WT1, a tumor-associated antigen overexpressed across a wide range of different tumor types and a known driver of leukocyte blasts in hematological cancers. Intellia’s first cell therapy tumor target is WT1 for the treatment of AML and other potential hematological malignancies, as well as for solid tumors.

Today’s presentation, titled "Exploiting Clonal Tracking of WT1-Specific T Cells to Generate a Library of Tumor-Specific T Cell Receptors (TCR), for TCR Gene Editing of Acute Leukemia," will be made by Eliana Ruggiero, Ph.D., Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Italy.

Additional In Vivo Data to be Presented at the 2019 ASGCT (Free ASGCT Whitepaper) Meeting

Intellia’s third oral presentation at the 2019 ASGCT (Free ASGCT Whitepaper) Meeting will take place later this week, on Thur., May 2, 2019. In a presentation titled "CRISPR/Cas9-Mediated Gene Knockout to Address Primary Hyperoxaluria," the company will provide information demonstrating successful independent knockout of two targets of interest, lactate dehydrogenase A (LDHA) and hydroxyacid oxidase 1 (HAO1), to address PH1 in a PH1 mouse model.

The data shows the continued progression of Intellia’s modular platform capability using CRISPR to knock out liver gene targets. The data being presented includes results from an ongoing collaboration with researchers at the University of Alabama at Birmingham.

CRISPR Therapeutics Provides Business Update and Reports First Quarter 2019 Financial Results

On April 29, 2019 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the first quarter ended March 31, 2019 (Press release, CRISPR Therapeutics, APR 29, 2019, View Source [SID1234535456]).

"This past quarter, we began an important new period for CRISPR Therapeutics with the treatment of the first patient in our clinical trial for CTX001 in hemoglobinopathies," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. "This is a significant landmark for the Company and we continue to enroll patients in our trials for both beta thalassemia and sickle cell disease. With the acceptance of our IND and CTA for CTX110, we look forward to the initiation of our clinical trials for our allogeneic CAR-T programs in the near-term and hope to bring other CAR-T programs to the clinic in the next six to twelve months."

Recent Highlights and Outlook

Hemoglobinopathies

Beta thalassemia
In April 2019, CRISPR Therapeutics and its partner, Vertex, announced that the U.S. Food and Drug Administration (FDA) had granted Fast Track Designation for CTX001, an investigational, autologous, gene-edited hematopoietic stem cell therapy, for the treatment of transfusion-dependent beta thalassemia (TDT). In February 2019, CRISPR and Vertex announced that the first patient had been treated with CTX001 in a Phase 1/2 clinical study of patients with TDT, marking the first company-sponsored use of a CRISPR/Cas9 therapy in a clinical trial. Enrollment in the Phase 1/2 study in patients with TDT is ongoing.

Sickle Cell Disease
The companies are also evaluating CTX001 for the treatment of sickle cell disease (SCD) and received Fast Track Designation for CTX001 from the FDA in January 2019 for SCD. The companies announced in February 2019 that the first patient had been enrolled in a Phase 1/2 clinical study of CTX001 in severe SCD in the U.S. and is expected to be infused with CTX001 in mid-2019. Enrollment in the Phase 1/2 study in patients with SCD is ongoing.
Immuno-Oncology

CTX110
Earlier this year, the FDA approved CRISPR Therapeutics’ Investigational New Drug (IND) application for CTX110, its wholly-owned allogeneic CAR-T cell therapy targeting CD19+ malignancies. Additionally, the Company has obtained approval from Health Canada for its Clinical Trial Application (CTA). CRISPR Therapeutics remains on track to initiate a Phase 1/2 trial to assess the safety and efficacy of CTX110 in the first half of 2019 and continues to work closely with various clinical sites to begin the trial. The Company’s proprietary CRISPR-based allogeneic CAR-Ts have the potential to create the next-generation of cell therapies that may have a superior product profile compared to current autologous therapies and allow accessibility to broader patient populations.

CRISPR Therapeutics continues to advance additional allogeneic CAR-T candidates including: CTX120, targeting B-cell maturation antigen (BCMA) for the treatment of multiple myeloma; and CTX130, targeting CD70 for the treatment of solid tumors and hematologic malignancies. Earlier this month, the Company presented preclinical data targeting multiple solid tumor types with anti-CD70 allogeneic CAR-T cells, further demonstrating consistent expression, durability, selectivity and potent cell killing. The Company also presented data targeting CD33 that showed potent preclinical activity against acute myeloid leukemia (AML) cells. These data were presented during poster sessions at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

CRISPR Therapeutics will present additional data at the upcoming 2019 American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting demonstrating the potential of CRISPR/Cas9 allogeneic CAR-T cell candidates for multiple oncology targets. CRISPR/Cas9 allogeneic CAR-T cells show consistently high percent CAR expression, while maintaining durable potency, low exhaustion, and lack of alloreactivity (#841). The Company will also present data evaluating homology-independent CRISPR/Cas9 off-target assessments methods (#134).
Corporate Development

The U.S. Patent Office issued four patents to Dr. Emmanuelle Charpentier, together with The Regents of the University of California and University of Vienna (collectively, CVC). Additionally, CVC was recently granted its third patent in Europe. These patents expand CVC’s wide-ranging CRISPR-Cas9 gene-editing patent portfolio.

Earlier this year, CRISPR Therapeutics announced strategic collaborations with StrideBio, Inc. and ProBioGen. The Company continues to examine new technologies and capabilities in support of existing programs.

In February, CRISPR Therapeutics proposed to elect John T. Greene and Katherine A. High, M.D. to its Board of Directors at the Company’s upcoming annual general meeting to be held later this year. Together, they will bring significant strategic and operational experience to CRISPR Therapeutics.
First Quarter 2019 Financial Results

Cash Position: Cash as of March 31, 2019, was $437.5 million, compared to $456.6 million as of December 31, 2018, a decrease of $19.1 million. Cash used in operations drove the decrease, offset by $25.7 million in net cash provided by financing activities during the quarter.

Revenues: Total collaboration revenues were $0.3 million for the first quarter of 2019 compared to $1.4 million for first quarter of 2018. CRISPR’s collaboration revenue is attributable to its research partnerships with Casebia and Vertex. Cost sharing on the Vertex co-development and co-promotion agreement related to hemoglobinopathies is not included in revenue, but instead as an offset to expense in R&D.

R&D Expenses: R&D expenses were $33.8 million for the first quarter of 2019 compared to $19.5 million for the first quarter of 2018. The increase was driven by headcount and services expense supporting the advancement of the hemoglobinopathies program, the broadening of the wholly-owned immuno-oncology portfolio, as well as increased investment in the Company’s CRISPR/Cas9 platform research.

G&A Expenses: General and administrative expenses were $14.9 million for the first quarter of 2019 compared to $8.8 million for the first quarter of 2018. The increase was driven by headcount-related expense and external professional and consulting service expense.

Net Loss: Net loss was $48.4 million for the first quarter of 2019 compared to a loss of $28.3 million for the first quarter of 2018, driven predominantly by increased R&D expense in the quarter.

Regeneron Announces Upcoming Investor Conference Presentations

On Apri 29, 2019 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it will webcast management presentations as follows (Press release, Regeneron, APR 29, 2019, View Source [SID1234535452]):

Bank of America Merrill Lynch 2019 Healthcare Conference at 8:00 a.m. Pacific Time (11:00 a.m. Eastern Time) on Wednesday, May 15, 2019
Barclays 2019 Biopharmaceuticals CEO/CFO Conference Call Series at 11:00 a.m. Eastern Time on Friday, May 17, 2019
UBS 2019 Global Healthcare Conference at 10:00 a.m. Eastern Time on Monday, May 20, 2019
The sessions may be accessed from the "Investors & Media" page of Regeneron’s website at View Source Replays of the conference call and webcasts will be archived on the Company’s website and will be available for 30 days.