On May 12, 2020 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to finding cures for blood cancers and serious blood diseases, reported positive topline results from its Phase 3 clinical study evaluating the safety and efficacy of omidubicel, an investigational advanced cell therapy in development as a potential life-saving treatment option for patients in need of bone marrow transplant (Press release, Gamida Cell, MAY 12, 2020, View Source [SID1234557616]). The median time to neutrophil engraftment was 12 days for patients randomized to omidubicel compared to 22 days for the comparator group (p<0.001). Neutrophil engraftment is a measure of how quickly the stem cells a patient receives in a transplant are established and begin to make healthy new cells, and rapid neutrophil engraftment has been associated with fewer infections and shorter hospitalizations.1

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Despite the curative potential of bone marrow transplant, it is estimated that more than 40 percent of eligible patients in the United States do not receive a transplant for various reasons, including the lack of a matched donor.2 Even for patients who do receive a transplant, treatment is not always effective and can lead to serious complications that can dramatically affect their quality of life.3 Omidubicel is intended to address the current limitations of bone marrow transplant by providing a therapeutic dose of stem cells while preserving the cells’ functional therapeutic characteristics.

"I’m very encouraged by the data from this rigorous, Phase 3 study that was conducted at more than 50 centers around the world, as there is a significant need for new bone marrow transplant graft modalities," said Mitchell Horwitz, M.D., principal investigator and professor of medicine at the Duke Cancer Institute. "These results have the potential to substantially move the field forward and represent an important step toward making stem cell transplantation more accessible and more successful for patients with lethal blood cancers. Shortening the time to engraftment is clinically meaningful, as it can reduce a patient’s time in the hospital and decrease likelihood of infection."

"Omidubicel is the first bone marrow transplant product to receive Breakthrough Therapy Designation from the U.S. Food and Drug Administration and has the potential to be the first FDA-approved bone marrow transplant graft. We are very pleased with the results of the Phase 3 data reported today, which move us one step closer toward bringing potentially curative therapies to patients. We expect to begin to submit our biologics license application for omidubicel to the FDA on a rolling basis in the fourth quarter of this year," stated Julian Adams, Ph.D., chief executive officer of Gamida Cell. "We deeply appreciate the participation of patients in this trial and the support we have received from investigators and their teams."

Topline Phase 3 Data

The international, multi-center, randomized Phase 3 study (NCT02730299) was designed to evaluate the safety and efficacy of omidubicel in patients with high-risk hematologic malignancies undergoing a bone marrow transplant compared to a comparator group of patients who received a standard umbilical cord blood transplant. The primary endpoint was time to neutrophil engraftment. The intent-to-treat analysis included 125 patients aged 12–65 years with acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome or lymphoma and was conducted at more than 50 clinical centers in the United States, Latin America, Europe and Asia. The demographics and baseline characteristics were well-balanced across the two study groups.

The study achieved its primary endpoint (p<0.001). In the intent-to-treat analysis, the median time to neutrophil engraftment was significantly shorter for patients who received omidubicel (12 days; 95% CI: 10-15 days) compared to the comparator group (22 days; 95% CI: 19-25 days). Omidubicel was generally well tolerated. Among patients who were transplanted per protocol, 96 percent of patients who received omidubicel achieved successful neutrophil engraftment, compared to 88 percent of patients in the comparator group.

"We are pleased with the outcome of this global, well-designed study in patients with life-threatening blood cancers who were in need of a bone marrow transplant and did not have an available matched donor," said Ronit Simantov, M.D., chief medical officer of Gamida Cell. "Importantly, these data confirmed the results from our earlier Phase 1/2 clinical study and demonstrated that patients who received omidubicel had more rapid recovery of neutrophils, which are key infection-fighting white blood cells."

The data reported today are consistent with results from a multi-center, Phase 1/2 study in 36 patients with advanced hematologic malignancies, which showed that patients treated with omidubicel demonstrated more rapid neutrophil engraftment compared to a concurrent cohort of 146 patients treated with standard umbilical cord blood as reported by the Center for International Blood and Bone Marrow Transplant Research.4 In the Phase 1/2 study, the median time to engraftment was 11.5 days (95% CI: 9-14 days) for omidubicel recipients compared to 21 days (95% CI: 20-23 days) for the CIBMTR cohort (p<0.001).

Gamida Cell expects to report full efficacy and safety results at a medical conference later this year.

Conference Call Information

Gamida Cell will host a conference call today, May 12, 2020, at 8:30 a.m. ET to discuss the Phase 3 study results. A live webcast of the conference call can be accessed in the "Investors" section of Gamida Cell’s website at www.gamida-cell.com. To participate in the live call, please dial 1-866-930-5560 (domestic toll-free), 1-409-216-0605 (international) and refer to conference ID number 5454076. A recording of the webcast will be available approximately two hours after the event, for approximately 30 days.

About Omidubicel

Omidubicel, the company’s lead clinical program, is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant solution for patients with hematologic malignancies (blood cancers). Omidubicel is the first bone marrow transplant product to receive Breakthrough Therapy Designation from the U.S. Food and Drug Administration and has also received Orphan Drug Designation in the U.S. and EU. In both Phase 1/2 and Phase 3 clinical studies, omidubicel demonstrated rapid and durable time to engraftment and was generally well tolerated. Omidubicel is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia.5 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 omidubicel. For more information on clinical trials of omidubicel, please visit www.clinicaltrials.gov.

Omidubicel is an investigational therapy, and its safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

On May 12, 2020 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, reported that management will present at the Bank of America 2020 Health Care Conference on Thursday, May 14 at 4:20 p.m. ET (Press release, Sangamo Therapeutics, MAY 12, 2020, View Source [SID1234557615]).

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The audio presentation will be webcast live and may be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations.

On May 12, 2020 INOVIO (NASDAQ:INO) reported that Dr. J. Joseph Kim, President and CEO, along with other members of management will present in a fireside discussion at the RBC Capital Markets Global Healthcare Conference on Tuesday, May 19, 2020 at 2:30 p.m. Eastern Time (Press release, Inovio, MAY 12, 2020, View Source [SID1234557613]).

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This fireside discussion will be held virtually and a live webcast may be accessed by visiting Inovio’s website at View Source Archived versions of the presentations will be made available through the INOVIO Investor Relations Events page.

On May 12, 2020 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported two poster presentations at the virtual 23rd Annual Meeting of the American Society of Gene & Cell Therapy ("ASGCT"), being held May 12-15, 2020 (Press release, Mustang Bio, MAY 12, 2020, View Source [SID1234557612]).

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Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We are extremely pleased with the strides forward that our researchers have made in gaining greater insights into our innovative CS1 chimeric antigen receptor (CAR) T cell therapy (MB-104), which we previously licensed from City of Hope. We commend them on their poster presentations at ASGCT (Free ASGCT Whitepaper) and look forward to learning more as they continue their research to optimize our clinical trials."

Details on the poster presentations are as follows:

Title: CS1 Targeted CAR-T Cells (MB-104) for the Treatment of Multiple Myeloma Shows Antitumor Activity Sparing Normal T-Cells Despite the Common Expression of CS1
Session: Cell Therapies
Abstract number: 421
Date and Time: Tuesday, May 12, 2020, 5:30 PM-6:30 PM ET
Room: Exhibit Hall C & D
Authors: Nathan Gumlaw, Aviva Joseph, James Edinger, Ekta Patel, Research and Translational Sciences, Mustang Bio, Worcester, MA

This poster describes researchers’ investigation into the impact of MB-104 on CS1 positive and negative cells in vitro, as well as T cells due to shared CS1 antigen expansion. The researchers demonstrated MB-104 does not confer biologically significant fratricide and can be successfully manufactured as evident by viability, growth kinetics and fold expansion, despite the shared antigen expression between tumor cells and T cells. CS1 positive T cells are present in culture during the expansion of MB-104, suggesting absence of fratricide. Finally, MB-104 can induce potent anti-tumor cell lysis and proliferates in response to tumor cells but not primary T cells expressing CS1. Taken together, their results demonstrate MB-104 is a novel CS1-targeting CAR T that shows potent anti-tumor cell lysis but spares normal T cells, despite the shared CS1 antigen expression.

Title: Development of an Immunohistochemistry Assay for the Detection of CS-1 Expression in Multiple Myeloma Patients
Session: Pharmacology/Toxicology Studies or Assay Development
Abstract number: 897
Date and Time: Wednesday, May 13, 2020, 5:30 PM-6:30 PM ET
Room: Exhibit Hall C & D
Authors: Bethany Biron Girard, James Edinger, Ekta Patel, Translational Sciences, Mustang Bio, Worcester, MA

This poster details a study in which researchers evaluated commercially available CS1 antibodies for IHC and identified the best clone with high specificity for CS1 to improve screening subjects for CS1 positive tumor expression prior to treatment and correlate efficacy with antigen expression. The researchers, for the first time, developed and optimized a robust immunohistochemistry assay for the assessment of CS1 expression in bone marrow core biopsy samples and plasmacytoma solid tumor samples from multiple myeloma ("MM") patients, which can be used for enrollment into Mustang’s CS1 CAR T clinical trials.

For more information, including abstracts, please visit the ASGCT (Free ASGCT Whitepaper) meeting website at View Source

On May 12, 2020 Seattle Genetics, Inc. (Nasdaq:SGEN) reported that the Swiss Agency for Therapeutic Products (Swissmedic) has granted approval for TUKYSA (tucatinib) tablets in combination with trastuzumab and capecitabine, for the treatment of patients with metastatic HER2-positive breast cancer, who have previously received two or more anti-HER2 regimens in any setting, including trastuzumab, pertuzumab and trastuzumab-emtansine (T–DM1) (Press release, Seattle Genetics, MAY 12, 2020, View Source [SID1234557608]).

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The application for TUKYSA approval was reviewed by Swissmedic as part of Project Orbis, an initiative of the U.S. Food and Drug Administration (FDA) Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among participating international regulatory agencies in Canada, Australia and Singapore. On April 17, the FDA approved TUKYSA in the U.S. under the FDA’s Real-Time Oncology Review (RTOR) pilot program, four months prior to its action date, and represented the first new drug approved under Project Orbis.

"We’re grateful to Swissmedic for their collaboration through FDA’s Project Orbis in approving this important new medicine in Switzerland," said Jennifer Stephens, Vice President of Regulatory Affairs at Seattle Genetics. "We’re committed to bringing new targeted therapies to patients, and we are excited about this important first step toward making TUKYSA available to patients in Switzerland."

TUKYSA is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.i,ii

The approval is based on results from the pivotal trial HER2CLIMB, a randomized (2:1), double-blind, placebo-controlled trial that enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1). The study results were published inThe New England Journal of Medicinein December 2019.

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. In 2018, more than two million new cases of breast cancer were diagnosed worldwide, including 522,513 in Europe. iii Between 15 and 20 percent of breast cancer cases are HER2-positive.iv Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.v,vi,vii Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.viii,ix,x

About TUKYSA (tucatinib)

TUKYSA is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.xi In the U.S., TUKYSA is approved in combination with trastuzumab and capecitabine for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

Important U.S. Safety Information

Warnings and Precautions

Diarrhea – TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death. In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 12% with Grade 3 diarrhea and 0.5% with Grade 4 diarrhea. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. The median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to dose reductions of TUKYSA in 6% of patients and discontinuation of TUKYSA in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB.
If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA.

Hepatotoxicity – TUKYSA can cause severe hepatotoxicity. In HER2CLIMB, 8% of patients who received TUKYSA had an ALT increase >5 × ULN, 5% had an AST increase >5 × ULN, and 1.5% had a bilirubin increase >3 × ULN (Grade ≥3). Hepatotoxicity led to dose reduction of TUKYSA in 8% of patients and discontinuation of TUKYSA in 1.5% of patients.
Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA.

Embryo-Fetal Toxicity – TUKYSA can cause fetal harm. Advise pregnant women and females of reproductive potential risk to a fetus. Advise females of reproductive potential, and male patients with female partners of reproductive potential, to use effective contraception during TUKYSA treatment and for at least 1 week after the last dose.
Adverse Reactions

Serious adverse reactions occurred in 26% of patients who received TUKYSA. Serious adverse reactions in ≥2% of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock.

Adverse reactions led to treatment discontinuation in 6% of patients who received TUKYSA; those occurring in ≥1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led to dose reduction in 21% of patients who received TUKYSA; those occurring in ≥2% of patients were hepatotoxicity (8%) and diarrhea (6%).

The most common adverse reactions in patients who received TUKYSA (≥20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.

Lab Abnormalities

In HER2CLIMB, Grade ≥3 laboratory abnormalities reported in ≥5% of patients who received TUKYSA were: decreased phosphate, increased ALT, decreased potassium, and increased AST. The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

Drug Interactions

Strong CYP3A or Moderate CYP2C8 Inducers: Concomitant use may decrease TUKYSA activity. Avoid concomitant use of TUKYSA.
Strong or Moderate CYP2C8 Inhibitors: Concomitant use of TUKYSA with a strong CYP2C8 inhibitor may increase the risk of TUKYSA toxicity; avoid concomitant use. Increase monitoring for TUKYSA toxicity with moderate CYP2C8 inhibitors.
CYP3A Substrates: Concomitant use may increase the toxicity associated with a CYP3A substrate. Avoid concomitant use of TUKYSA where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP3A substrate dosage.
P-gp Substrates: Concomitant use may increase the toxicity associated with a P-gp substrate. Consider reducing the dosage of P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicity.
Use in Specific Populations

Lactation: Advise women not to breastfeed while taking TUKYSA and for at least 1 week after the last dose.
Renal Impairment: Use of TUKYSA in combination with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (CLcr < 30 mL/min), because capecitabine is contraindicated in patients with severe renal impairment.
Hepatic Impairment: Reduce the dose of TUKYSA for patients with severe (Child-Pugh C) hepatic impairment.
For more information, please see the full Prescribing Information for TUKYSA here.