On February 25, 2019 Gamida Cell Ltd. (Nasdaq:GMDA), a leading cellular and immune therapeutics company, reported financial results for the fourth quarter and full year ended December 31, 2018, and provided a business update, which highlights the company’s progress advancing its clinical development candidates: NiCord, an investigational advanced cell therapy in Phase 3 clinical development designed to enhance and expand the life-saving benefits of hematopoietic stem cell (bone marrow) transplant, and NAM-NK, an investigational, cell-based cancer immunotherapy in Phase 1 development in patients with non-Hodgkin lymphoma and multiple myeloma (Press release, Gamida Cell, FEB 25, 2019, View Source [SID1234533637]).

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!

Gamida Cell continues to anticipate completing patient enrollment in the Phase 3 study of NiCord by the end of this year with topline data anticipated in first half of 2020. The international, randomized, multi-center study is designed to evaluate the safety and efficacy of NiCord compared to standard umbilical cord blood for allogeneic bone marrow transplant in approximately 120 patients with no available matched donor. Additionally, the company continues to make progress in its NAM-NK program, and expects to initiate a multi-center Phase 1/2 study of NAM-NK in patients with blood cancer in 2020.

"We are off to a strong start this year and are making meaningful progress across every dimension of our company. The data presented last week at the TCT Annual Meeting demonstrates the potential for NiCord to offer a new cell therapy option for patients in need of a bone marrow transplant," stated Julian Adams, Ph.D., chief executive officer at Gamida Cell. "Additionally, our collaboration with Be The Match BioTherapies and the appointment of Tom Klima as chief commercial officer underscore our commitment to advancing our clinical development plans and beginning commercial readiness activities for the potential approval and launch of NiCord."

Dr. Adams continued, "We are committed to leveraging the transformative potential of our proprietary nicotinamide-, or NAM-based, cell expansion technology, to deliver a multi-product pipeline. Last week, we presented encouraging data from our ongoing Phase 1 study of NAM-NK in patients with non-Hodgkin lymphoma and multiple myeloma, and the emerging clinical profile suggests it has the potential to address some of the limitations of currently available cell therapies. In addition, we have demonstrated the ability to cryopreserve our NK cells in a laboratory setting, and we are working to scale up our manufacturing process to enable the ability to evaluate multiple doses and schedules of NAM-NK therapy in a multi-center, Phase 1/2 clinical study next year."

Recent Company Highlights:

Reported additional immune reconstitution data for NiCord supporting clinical potential for bone marrow transplant: In February, translational data from the completed Phase 1/2 study of NiCord were reported at the 2019 Transplantation & Cellular Therapy (TCT) Meetings of American Society for Blood and Marrow Transplantation and Center for International Blood and Marrow Transplant Research demonstrating that recipients who received NiCord had rapid and robust reconstitution of key immune cells. Successful immune reconstitution is an important factor in the recovery of patients undergoing bone marrow transplant.
Reported initial data from Phase 1/2 study of NiCord in severe aplastic anemia: At the 2019 TCT Annual meeting, data were reported from the ongoing Phase 1/2 study of NiCord in patients with severe aplastic anemia. In the initial cohort of three patients, all successfully underwent a bone marrow transplant consisting of NiCord plus a haploidentical stem cell graft. The rapid cord engraftment, sustained hematopoiesis and accelerated immune recovery in treatment refractory observed in these patients enable the initiation of a second cohort of patients to be treated with NiCord as a stand-alone graft. Patient enrollment in the second cohort is expected to begin in the first half of 2019.
Announced encouraging data from Phase 1 study of NAM-NK in non-Hodgkin Lymphoma and multiple myeloma: During the 2019 TCT Annual Meeting, data reported from the ongoing Phase 1 study of NAM-NK in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) demonstrated that NAM-NK was clinically active, with three complete responses observed in patients with NHL and one complete response in a patient with MM. These data, along with safety data showing that NAM-NK was generally well tolerated, support continued clinical development, and Gamida Cell is planning to initiate a multi-center, Phase 1/2 clinical study of NAM-NK in patients with blood cancers in 2020.
Entered into agreement with Editas Medicine to evaluate potential to gene edit NAM-NK cells: In February, Gamida Cell announced an agreement with Editas Medicine, Inc. to evaluate the potential use of Editas Medicine’s CRISPR technology to edit NAM-NK cells. Through this agreement, the companies aim to rapidly discover optimized NAM-NK cells that could be used to improve the treatment of blood cancers and solid tumors.
Formed strategic collaboration with Be The Match BioTherapies: In January 2019, both organizations announced a collaboration to expand the use of bone marrow transplant to treat hematologic malignancies and serious blood disorders. Under the terms of the collaboration agreement, the organizations will explore opportunities to work together across Gamida Cell’s ongoing clinical development program for NiCord, including the ongoing Phase 3 clinical study. Be The Match BioTherapies has an extensive history of involvement in the delivery of cord blood units for transplant and broad access to cord blood banks globally.
Appointed Thomas Klima as Chief Commercial Officer: In January, the company announced the appointment of Thomas Klima as Chief Commercial Officer. Mr. Klima brings nearly 20 years of global experience in the pharmaceutical industry with expertise in cellular therapy, hematology, oncology and transplantation. During his career, he has played key roles in building commercial organizations and leading multiple successful product launches.
Appointed Nurit Benjamini to Board of Directors: In January, the company appointed Nurit Benjamini to Gamida Cell’s board of directors and chair of the board’s audit committee. Ms. Benjamini has served as chief financial officer of TabTale Ltd. since 2013. Previously, she held a number of chief financial officer positions, including at Wix.com Ltd., Sigma Designs Israel Ltd. and Compugen Ltd.
Anticipated 2019-2020 Milestones
Gamida Cell’s anticipated program milestones in 2019-2020 are as follows:

Nicord

Initiate Cohort 2 in the Phase 1/2 study evaluating NiCord as stand-alone graft in severe aplastic anemia in the first half of 2019
Complete enrollment in Phase 3 study of NiCord in patients with hematologic malignancies in the second half of 2019
Report topline data from the Phase 3 study of NiCord in patients with hematologic malignancies in the first half of 2020
Complete BLA filing for NiCord in hematologic malignancies in the second half of 2020, should Phase 3 data be positive
NAM-NK

Complete patient enrollment in the ongoing Phase 1 study in the second half of 2019
Present additional data at a medical meeting in the second half of 2019
Initiate multi-center, Phase 1/2 clinical study in 2020
Fourth Quarter and Full Year 2018 Financial Results:

At December 31, 2018, Gamida Cell had total cash, cash equivalents and available-for-sale securities of $60.7 million, compared to $41.1 million at December 31, 2017.
Research and Development expenses in 2018 were $22.0 million, compared to $15.0 million in 2017. The increase was attributable mainly to a $5.4 million increase in clinical activities relating to the advancement of Gamida Cell’s clinical programs as well as an increase of $1.6 million in other R&D expenses.
General and administrative expenses were $11.6 million in 2018, compared to $4.5 million in 2017. The increase was attributable mainly to a $2.9 million increase in expenses related to expanding the management team and establishing the U.S. headquarters, an increase of $2.0 million in non-cash stock-based compensation expenses, and $2.2 million in professional services expenses incurred during the IPO process, rent and other expenses.
Finance expenses, net, were $19.2 million in 2018, compared to $0.5 million in income, in 2017. The increase was primarily due to non-cash expenses resulting from revaluation of warrants and the revaluation of royalty-bearing grant IIA liability.
Net loss for 2018 was $52.9 million, compared to a net loss of $19.1 million for 2017.
2019 Financial Guidance
Gamida Cell expects cash used for ongoing operating activities in 2019 to range from $35-$40 million, reflecting anticipated expenditures to advance the company’s clinical programs.

Gamida Cell expects that its cash, cash equivalents and available-for-sale securities will support the company’s capital needs through the data readout for the Phase 3 clinical study of NiCord, which is expected in the first half of 2020. This cash runway guidance is based on the company’s current operational plans and excludes any additional funding that may be received or business development activities that may be undertaken.

About NiCord
NiCord, the company’s lead clinical program, is under development as a universal bone marrow transplant solution for patients with high-risk hematologic malignancies. NiCord has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration, making it the first bone marrow transplant alternative to receive this designation. It has also received U.S. and EU orphan drug designation. A Phase 3 clinical study evaluating NiCord in patients with leukemia and lymphoma is ongoing in the United States, Europe and Asia.1 NiCord is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia.2 The aplastic anemia investigational new drug application is currently filed with the FDA under the brand name CordIn, which is the same investigational development candidate as NiCord. For more information on clinical trials of NiCord, please visit www.clinicaltrials.gov.

About NAM-NK
Gamida Cell applied the capabilities of its NAM-based cell expansion technology to highly functional NK cells to develop NAM-NK, an innate immunotherapy for the treatment of hematologic and solid tumors in combination with standard of care antibody therapies. NAM-NK addresses key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs of NK cells expanded in culture. NAM-NK is in Phase 1 development through an investigator-sponsored study in patients with refractory non-Hodgkin lymphoma and multiple myeloma.3

NAM-NK and NiCord are investigational therapies, and their safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

On February 25, 2019 Magenta Therapeutics (NASDAQ:MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, reported that the Company highlighted preclinical research on its targeted conditioning programs in four presentations and posters at the Transplant and Cellular Therapy (TCT) annual meeting (Press release, Magenta Therapeutics, FEB 25, 2019, View Source [SID1234533636]).

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!

Patients currently undergoing stem cell transplant or stem cell gene therapy are first prepared, or conditioned, with non-specific, genotoxic chemotherapy alone or in combination with total body irradiation. This process is associated with significant side effects, including infertility and mortality risks, which can prevent many eligible patients from undergoing a stem cell transplant or gene therapy. Magenta is developing a portfolio of targeted antibody drug conjugates (ADCs), including non-genotoxic agents, that selectively remove the specific cells needed to enable a successful transplant or gene therapy procedure without the toxicities of chemotherapy and radiation. Magenta’s C100 program targets CD45, expressed on both stem and immune cells, with the goal of enabling stem cell transplant in blood cancer and autoimmune diseases. Magenta’s C200 program targets CD117, expressed on stem cells, with potential applicability as a conditioning agent before gene therapy for genetic diseases and stem cell transplant for blood cancers.

"Stem cell transplant and gene therapy are potential cures for many diseases, including sickle cell disease, blood cancers, and autoimmune diseases, such as multiple sclerosis and systemic sclerosis. However, the toxicity of the current conditioning regimens prevents a significant percentage of patients from considering a transplant or gene therapy and requires the patients who do undergo the procedure to trade their disease for the prospect of infertility, organ damage, secondary cancers and even death," said Michael Cooke, Ph.D., Chief Scientific Officer, Magenta Therapeutics. "Data in non-human primates from Magenta’s two distinct lead conditioning programs show potent and selective depletion of the target cells, and the ADCs were well tolerated. Based on these promising data, we selected a development candidate for the C200 program and have moved into IND-enabling studies. We expect to declare a candidate for the C100 program this year and move into IND-enabling studies in 2020."

Non-Genotoxic Conditioning Using Amanitin Antibody-Drug Conjugates Targeting CD45 Effectively Deplete Human and Non-Human Primate Hematopoietic Stem Cells and Immune Cells (C100 Program)

Key results, presented by Rahul Palchaudhuri, Ph.D., Magenta Therapeutics:

A single dose of an anti-CD45 ADC achieved efficient depletion of immune cells in the periphery and hematopoietic stem cells in the bone marrow in preclinical models.
An anti-CD45 amanitin ADC with engineered fast half-life demonstrated potent depletion of peripheral immune cells as well as immune cells and hematopoietic stem cells in the bone marrow of non-human primates.
An anti-CD45 amanitin ADC with engineered fast half-life demonstrated potent stem and immune cell depletion and rapid clearance, providing optimal pharmacokinetics for patient preparation for stem cell transplant.
These ADCs were well tolerated at the efficacious doses.
Simultaneous depletion of immune and hematopoietic stem cells using an anti-CD45 ADC with rapid clearance may enable safer conditioning for allogeneic transplant and enable an immune-reset in autoimmune disease transplantation, broadening patient access to this potentially curative therapy.
Magenta plans to optimize the anti-CD45 ADC and select a development candidate in 2019, with IND-enabling studies to begin in 2020.
Magenta is testing anti-CD45 ADCs in preclinical models of autoimmune disease, with data expected later in 2019.
A CD117-Amanitin Antibody Drug Conjugate Effectively Depletes Human and Non-Human Primate Hematopoietic Stem and Progenitor Cells: Targeted Non-Genotoxic Conditioning for Bone Marrow Transplant (C200 Program)

Key results, presented by Brad Pearse, Ph.D., Magenta Therapeutics:

An anti-CD117 ADC conjugated with amanitin potently depleted both human and non-human primate hematopoietic stem cells and progenitors in vivo.
An anti-CD117 amanitin ADC with engineered fast half-life demonstrated potent stem cell depletion and rapid clearance, representing optimal pharmacokinetics and pharmacodynamics for patient preparation for stem cell transplant or gene therapy.
The ADCs were well tolerated at the efficacious doses.
Potent and selective depletion of stem cells with rapid clearance of the ADC has the potential to provide a significant improvement over current approaches to patient preparation prior to stem cell transplant and gene therapies, broadening patient access to curative therapies.
Magenta has declared a lead for development for the C200 program and moved into IND-enabling studies.
Magenta is undertaking studies of C200 in preclinical models for gene therapy conditioning, with data expected later this year.
Single Doses of Antibody Drug Conjugates (ADCs) Targeted to CD117 or CD45 Have Potent In Vivo Anti-Leukemia Activity and Survival Benefit in Patient-Derived AML Models

Key results, presented by Jennifer Proctor, Magenta Therapeutics:

CD117 is expressed on human hematopoietic stem and progenitor cells and on leukemia cells in 80% of patients with acute myeloid leukemia (AML) and in 65% of patients with myelodysplastic syndromes (MDS); CD45 is expressed on all lympho-hematopoietic cells in many blood cancers.
Both the anti-CD117 amanitin ADC and the anti-CD45 amanitin ADC demonstrated potent killing of human hematopoietic stem cells and leukemia cell lines in vitro.
A single dose of either ADC demonstrated potent in vivo anti-leukemia activity in mice bearing established human leukemia cell lines.
Both ADCs significantly improved the survival of mice engrafted with human leukemia cells from AML patients, which included leukemias that were resistant to multiple lines of therapy.
Magenta Therapeutics’ C200 and C100 programs are designed with the dual intent of selectively eliminating the necessary cells to enable a successful transplant and reducing disease burden.
Magenta continues to progress ADC-based conditioning approaches targeting CD45 and CD117 toward the clinic.
CD45-Targeted Antibody-Drug Conjugate Plus Post-Transplant Cytoxan is Sufficient to Enable Allogeneic Bone Marrow Transplant in a Minor Mismatch Mouse Model (C100 Program)

Key results, presented by Sharon Hyzy, M.S., Magenta Therapeutics:

ADCs targeted to mouse CD45 have been shown to effectively condition immunocompetent mice for autologous stem cell transplant.
To investigate the utility of a murine-specific tool ADC conjugated to saporin to enable allogenic transplant, Magenta assessed this ADC as a single agent or in combination with immunosuppressive agents to facilitate transplant in a murine allogeneic transplant model.
A single dose of anti-CD45 saporin ADC, when combined with post-transplant cyclophosphamide to prevent graft-versus-host-disease, enabled successful engraftment across minor histocompatibility antigens.
The anti-CD45 saporin ADC was more effective than an unconjugated anti-CD45 antibody, pre-transplant cyclophosphamide, or sublethal irradiation in combination with post-transplant cyclophosphamide.
Magenta continues to investigate additional linker-toxins as well as ADC-based conditioning in multiple allogeneic mouse models.

On February 25, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported topline results from the Phase III COLUMBA study (MMY3012) of subcutaneous (SC) versus intravenous (IV) daratumumab for patients with relapsed or refractory multiple myeloma (Press release, Genmab, FEB 25, 2019, View Source [SID1234533635]). The results showed that SC administration of daratumumab co-formulated with recombinant human hyaluronidase PH20 is non-inferior to IV administration of daratumumab with regard to the co-primary end points of overall response rate (ORR) and Maximum Trough concentration (Ctrough) of daratumumab on day 1 of the third treatment cycle.

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!

The ORR for patients treated with SC daratumumab was 41.1% (n=263) versus 37.1% in patients treated with IV daratumumab (n= 259). The lower limit of the 95% Confidence Interval (CI) for the ratio of the two met the specified non-inferiority criterion for this co-primary endpoint. The geometric mean of Ctrough for patients treated with SC daratumumab was 499 mg/mL (n=149) versus 463 mg/mL in patients treated with IV daratumumab (n= 146). The lower limit of the 95% CI for the ratio of the two met the specified non-inferiority criterion for this co-primary endpoint.

No new safety signals were detected and Janssen Biotech, Inc., which licensed daratumumab from Genmab in 2012, will discuss the potential for a regulatory submission for this formulation with health authorities, and plans to submit the data to an upcoming medical conference and for publication in a peer-reviewed journal.

"With the data from each of the key clinical studies we learn more about the difference that daratumumab potentially can make to the lives of patients suffering with multiple myeloma. I am particularly excited about the results from this study as it may support a much quicker and far more convenient administration of daratumumab, which would provide an important benefit for many patients and their families," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the COLUMBA (MMY3012) study
The Phase III trial (NCT03277105) is a randomized, open-label, parallel assignment study that includes 522 adults diagnosed with relapsed and refractory multiple myeloma. Patients were randomized to receive either: SC daratumumab, as 1800 mg daratumumab with rHuPH20 2000 U/mL once weekly in Cycle 1 and 2, every two weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study or 16 mg/kg IV daratumumab once weekly in Cycle 1 and 2, every two weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The co-primary endpoints of the study are ORR and Maximum trough of daratumumab (Ctrough; defined as the serum pre dose concentration of daratumumab on Cycle 3 Day 1).

About DARZALEX(daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United Stated, Europe and Japan. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.

On February 25, 2019 Marker Therapeutics, Inc. (NASDAQ:MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported updated data from four clinical trials using the Company’s multi-antigen targeted T cell (MultiTAA) therapies (Press release, Marker Therapeutics, FEB 25, 2019, View Source;utm_medium=email&utm_campaign=investor_alerts&utm_content=Marker+Therapeutics+Announces+Clinical+Update+at+the+Transplantation+%26+Cellular+Therapy+Meetings+of+ASBMT+and+CIBMTR+2019 [SID1234533634]). The data was reviewed in oral and poster presentations at the Transplantation & Cellular Therapy Meetings of ASBMT and CIBMTR 2019 which took place in Houston, TX from February 20-24. Among the highlights, were results from an ongoing study including patients with acute myeloid leukemia (AML), which were reviewed in an oral presentation by Dr. Premal Lulla, M.B.B.S., Assistant Professor of Medicine, Baylor College of Medicine.

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!

"We continue to be highly encouraged by the clinical results we’ve seen to date with our MultiTAA therapies. In AML, we believe we are seeing increasing evidence of meaningful therapeutic benefit for patients with limited treatment alternatives. Our MultiTAA therapy appears to be safe and well-tolerated with the potential to mediate a meaningful anti-tumor effect, in addition to demonstrating a compelling correlation between therapeutic responses, with superior in vivo expansion of our T cells," said Peter L. Hoang, President & CEO of Marker Therapeutics. "Similarly, the studies ongoing in acute lymphoblastic leukemia, or ALL, lymphoma and multiple myeloma continue to demonstrate positive results, and are supportive of the data we presented at ASH (Free ASH Whitepaper) in December, importantly with no additional disease relapses. Overall, this data update and our update at ASH (Free ASH Whitepaper) 2018 in December collectively have increased our total reported number of patients to 78 as compared to the 57 patients we had reported as of November."

AML Study Results

In Arm A of the AML study, 13 patients at Baylor College of Medicine were dosed with MultiTAA T cells as a maintenance therapy after receiving allogeneic stem cell transplant. Results demonstrated:

11 out of 13 patients remain alive, ranging from 6 weeks to 2.5 years post-infusion. Nine of these patients have never relapsed after MultiTAA therapy and continue to remain in complete remission (CR), durable between 6 weeks to 2.5 years;
Two patients saw local relapse in the central nervous system, but in both cases these patients were successfully treated with local therapy alone;
One patient saw extramedullary relapse and was subsequently treated in the active disease arm (Arm B) of the trial, generating a CR that was durable for 13 months; and
One patient relapsed 8 months after receiving MultiTAA T cells but following a second allogeneic stem cell transplant this patient remains alive in relapse 1.5 years following his initial T cell infusion.
In Arm B of the AML study, 6 patients suffering from active disease with relapsed/refractory (r/r) AML have been treated, with 1 patient having been treated twice for active disease with MultiTAA T cells;

2 patients were non-responsive to MultiTAA therapy and progressed with r/r disease;
1 patient developed a complete response (CR), which was durable for 13 months; and
1 patient developed a partial response (PR) that enabled that patient to receive a second allogeneic stem cell transplant;
The patient who developed a partial response saw significant tumor debulking, with circulating blasts reduced from over 50% to 15%.
2 additional patients who did not meet partial response criteria experienced disease stabilization enabling a 2-month delay to next-line therapy
Of these patients with disease stability, one patient was sufficiently stabilized to enable that patient to receive a second allogeneic stem cell transplant. The second transplant eliminated the patient’s MultiTAA T cells. This patient was given a second dose of MultiTAA T cells after initial disease relapse after the second transplant, but progressed to another line of therapy prior to any evaluable response assessment to the subsequent dose of MultiTAA T cells;
The other patient who had disease stability saw significant reduction in tumor burden, with a reduction in circulating blasts from 70% prior to infusion of MultiTAA T cells, to approximately 45% circulating blasts after MultiTAA therapy.
For patients in Arm B, overall survival ranged from 4 to 21 months after T cell infusions.
ALL Results

In addition to data from ongoing lymphoma and multiple myeloma trials, also presented in an oral presentation at the meeting were updated results from an ongoing study in ALL. Updates from this trial included:

Patients are now up to 28 months in CCR (Continued Complete Remission);
The only patient who has experienced relapse was a patient who displayed mixed donor/recipient chimerism after transplant, but remained in CCR for 6 months prior to relapse;
Patients that remain in CCR have been durable for between 4 to 28 months, with a median duration of 16 months.
"We are very excited about the results we are seeing in our early clinical trials. For patients with r/r AML, we believe that MultiTAA therapies may produce meaningful improvements in overall survival of patients who historically have had a dire prognostic outlook," stated Mythili Koneru, Senior Vice President of Clinical Development at Marker Therapeutics. "In adjuvant settings for patients currently in remission, I believe our early clinical results suggest that we may be providing significant additional protection against relapse and disease recurrence."

On February 25, 2019 CRISPR Therapeutics (NASDAQ: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the fourth quarter and full year ended December 31, 2018 (Press release, CRISPR Therapeutics, FEB 25, 2019, View Source [SID1234533633]).

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!

"This past year was truly transformational for CRISPR Therapeutics as we achieved milestones across our key programs in β-thalassemia, sickle cell disease and immuno-oncology. We’re pleased with the progress we’ve made in 2018, especially in clinical execution and the expansion of our development pipeline. We also strengthened our team with key new hires, positioning us well as we advance to the next stage of development. This progress brings us closer to realizing our mission of bringing transformative therapies to patients with serious diseases," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics.

Dr. Kulkarni added: "Over the next two years, we expect to generate data from clinical trials across multiple indications as we bring CRISPR technology to patients. In addition, we are making deliberate steps to scale the Company as we advance programs across a number of therapeutic areas while continuing to bolster our proprietary CRISPR platform."

Recent Highlights and Outlook

Hemoglobinopathies

° β-thalassemia
CRISPR Therapeutics, together with its partner, Vertex, announced that the first patient has been treated with CTX001 in a Phase 1/2 clinical study of patients with transfusion-dependent beta thalassemia (TDT), marking the first company-sponsored use of a CRISPR/Cas9 therapy in a clinical trial. The Phase 1/2 open-label trial is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 18 to 35 with TDT, non-beta zero/beta zero subtypes. The first two patients in the trial will be treated sequentially and, pending data from these initial two patients, the trial will open for broader concurrent enrollment. The companies plan to target presentations of data at scientific conferences once there is sufficient data on multiple patients.

° Sickle Cell Disease
CRISPR Therapeutics, together with its partner, Vertex, are also investigating CTX001 for the treatment of severe sickle cell disease (SCD) and announced that the first patient has 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. The Phase 1/2 open-label trial is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 18 to 35 with severe SCD. Similar to the trial in beta thalassemia, the first two patients in the trial will be treated sequentially prior to broader concurrent enrollment. The companies plan to target presentations of data at scientific conferences once there is sufficient data on multiple patients. CTX001 was recently granted Fast Track Designation by the U.S. Food and Drug Administration for the treatment of SCD.
Immuno-Oncology

° CRISPR Therapeutics is on track to initiate a clinical trial for CTX110, its wholly-owned allogeneic CAR-T cell therapy targeting CD19+ malignancies, in the first half of 2019. CRISPR/Cas9 has the potential to create the next-generation of CAR-T cell therapies that may have a superior product profile compared to current autologous therapies and allow accessibility to broader patient populations. The Company continues to advance two additional allogeneic CAR-T candidates; CTX120, targeting B-cell maturation antigen (BCMA) for the treatment of multiple myeloma; and CTX130, targeted towards CD70 for the treatment of both solid tumors and hematologic malignancies. In November, the Company presented a poster at the Society for Immunotherapy in Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting related to multiplex editing and production of allogeneic CAR-T therapies. Additionally, the Company presented a poster at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 Annual Meeting in December, highlighting further development and preclinical data for CTX120. The study showed maintained cytotoxic capacity over multiple in vitro re-challenges, demonstrating durable potency and reduced susceptibility to exhaustion.
Other Programs

° In September, CRISPR Therapeutics and ViaCyte, Inc. announced a collaboration focused on the discovery, development, and commercialization of gene-edited allogeneic stem cell derived islet cell progenitors which may offer curative benefit to patients with insulin-requiring diabetes. The combination of ViaCyte’s stem cell capabilities and CRISPR Therapeutics’ gene editing capabilities has the potential to enable a beta-cell replacement product that may deliver durable benefit to patients without the need for immune suppression.

° Earlier this year, CRISPR Therapeutics announced strategic collaborations with StrideBio, Inc. and ProBioGen. The Company’s collaboration with StrideBio expands upon an existing agreement to generate engineered AAV capsids with improved properties for in vivo gene editing programs and now includes additional undisclosed applications. CRISPR Therapeutics and ProBioGen announced a collaboration focused on the development of novel in vivo delivery modalities for CRISPR/Cas9 leveraging ProBioGen’s existing technology and expertise.

° In November, CRISPR Therapeutics and MaxCyte announced the expansion of an existing collaboration by entering into a non-exclusive commercial license agreement allowing CRISPR Therapeutics to deploy MaxCyte’s Flow Electroporation Technology to develop CRISPR/Cas9-based therapies in immuno-oncology. The collaboration builds on an existing agreement which allowed for the development of commercial therapeutics for hemoglobin-related diseases.
Company Building

° CRISPR Therapeutics continued to expand core capabilities in critical areas with the addition of key new talent across several functions.

° 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.
Fourth Quarter and Full Year 2018 Financial Results

Cash Position: Cash and cash equivalents as of December 31, 2018 were $456.6 million, compared to $239.8 million as of December 31, 2017, an increase of $216.8 million, which was primarily driven by the net proceeds of $307.1 million from the sale of shares in follow-on financing rounds executed in January and September of 2018, offset by the Company’s use of $96.2 million for operating activities.

Revenue: Total collaboration revenue was $0.1 million for the fourth quarter of 2018 compared to $32.3 million for fourth quarter of 2017, and $3.1 million for the year ended December 31, 2018, compared to $41.0 million for the year ended December 31, 2017. The decrease in annual revenue is primarily attributable to deferred revenue recognized in 2017 in conjunction with the execution of the Company’s collaboration agreement with Vertex. During 2018 and going forward, Vertex funding of hemoglobinopathies programs are categorized as a contra-expense as opposed to revenue.

R&D Expenses: R&D expenses were $28.8 million for the fourth quarter of 2018 compared to $20.0 million for the fourth quarter of 2017, and $113.8 million for the year ended December 31, 2018 compared to $69.8 million for the year ended December 31, 2017. The increase in expense for the year was driven by greater investment in CRISPR’s lead hemoglobinopathies program partnered with Vertex, one-time expense associated with beginning our ViaCyte collaboration and expenses from the Company’s wholly owned immuno-oncology and in vivo programs.

G&A Expenses: General and administrative expenses were $16.5 million for the fourth quarter of 2018 compared to $11.3 million for the fourth quarter of 2017, and $48.3 million for the year ended December 31, 2018 compared to $35.8 million for the year ended December 31, 2017. The increase in general and administrative expenses for the year was driven by increased professional services and employee-related costs associated with our growing organization.

Net Income/Loss: Net loss was $47.6 million for the fourth quarter of 2018 compared to income of $0.1 million for the fourth quarter of 2017, and net loss was $165.0 million for the year ended December 31, 2018 compared to a loss of $68.4 million for the year ended December 31, 2017.