On December 4, 2020 Y-mAbs Therapeutics, Inc. (Nasdaq: YMAB) (the "Company" or "Y-mAbs") a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer and Takeda Israel, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported that they have entered into an exclusive license and distribution agreement for the registration and commercialization in Israel of DANYELZA for the treatment of patients with relapsed/refractory high-risk neuroblastoma and omburtamab for the treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma (Press release, Y-mAbs Therapeutics, DEC 4, 2020, View Source [SID1234572168]). DANYELZA (naxitamab-gqgk) was approved by the U.S. FDA on November 25, 2020. Additionally, Y-mAbs plans to resubmit the amended BLA for omburtamab for the treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma to the FDA by the end of 2020 or in early 2021.

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Under the terms of the agreement, Takeda will employ its proven platform of sales, access, marketing and regulatory expertise to distribute DANYELZA and omburtamab, if approved, in the territory. The license and distribution agreement includes the State of Israel, West Bank and Gaza Strip. All other geographies worldwide remain with the Company. Financial details were not disclosed.

"We are very pleased to enter into this license and distribution agreement with Takeda, and now expect to see a treatment cluster established in the Middle East, thereby making DANYELZA and omburtamab, if approved, available to children with unmet medical needs in the region," said Thomas Gad, founder, Chairman and President at Y-mAbs.

Arie Kramer, General Manager at Takeda further notes, "Relapsed/refractory high-risk neuroblastoma and CNS/leptomeningeal metastasis from neuroblastoma are cancers for which there are currently no approved therapies in Israel, and we are excited to partner with Y-mAbs, making these compounds available and bringing new hopes to pediatric patients suffering from these devastating conditions in Israel."

Researchers at MSK developed DANYELZA and omburtamab, which are exclusively licensed by MSK to Y-mAbs. As a result of this licensing arrangement, MSK has institutional financial interests in the compounds and in Y-mAbs.

About DANYELZA (naxitamab-gqgk)
DANYELZA (naxitamab-gqgk) is indicated, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF"), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefits in a confirmatory trial. DANYELZA includes a Boxed Warning for serious infusion-related reactions, such as cardiac arrest and anaphylaxis, and neurotoxicity, such as severe neuropathic pain and transverse myelitis. See full Prescribing Information for complete Boxed Warning and other important safety information.

About Neuroblastoma

Neuroblastoma is a solid tumor of childhood that arises in the nervous system, outside of the brain. The clinical behavior of neuroblastoma is highly variable, with some tumors being easily treatable, but the majority being very aggressive. All patients are staged based on the International Neuroblastoma Staging System Committee ("INSS") system, ranging from stage 1 through stage 4S. All patients with stage 4 disease diagnosed after one year of age are classified in the high-risk category, where the neuroblastoma tumor cells have already metastasized to other sites in the body, such as the bone or bone marrow. Essentially all patients who have tumors with many copies, or amplification, of the MYCN oncogene also have high-risk disease, even if they do not have evidence of the tumor having spread.

On December 4, 2020 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported that three posters highlighting its drug development pipeline would be presented at the upcoming San Antonio Breast Cancer Conference (SABCS) to be held December 8 – 11, 2020 (Press release, Spectrum Pharmaceuticals, DEC 4, 2020, View Source [SID1234572164]).

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"We are pleased to have two scientific communications at SABCS on ROLONTIS (eflapegrastim) and the results of our Phase 2 study for Poziotinib in HER2+ metastatic breast cancer who have failed multiple lines of HER2 directed therapy," said Francois Lebel, M.D., Chief Medical Officer at Spectrum Pharmaceuticals. "We look forward to sharing these data with the medical and scientific community."

The three posters are listed below.

Poster Title: A Phase 2 study of poziotinib in patients with HER2-positive metastatic breast cancer previously treated with HER2 therapies
Authors: Adam Brufsky, M.D., Ph.D., et al.
Poster Number: PD1-07 (Spotlight Poster Discussion)
Poster Category: Breast Cancer treatment
Poster Section: Spotlight Poster Discussion 1
Poster Presentation Date/Time: December 9, 2020 4:00 PM – 5:15 PM CT

Poster Title: Pooled efficacy analysis from two Phase 3 studies in patients receiving eflapegrastim, a novel, long-acting granulocyte-colony stimulating factor, following TC for early stage breast cancer
Authors: Lee S. Schwartzberg, M.D., et al.
Poster Number: PS9-59
Poster Category: Psychosocial, Quality of Life and Educational Aspects
Poster Section: Poster Session 9
Poster Presentation Date/Time: Wednesday, December 9, 2020: 8:00 AM CT.

Poster Title: Open-label, Phase 1 study to evaluate duration of severe neutropenia after the same-day, varying dosing time schedules of eflapegrastim administration in patients with breast cancer receiving docetaxel and cyclophosphamide (NCT04187898)
Authors: Lee S. Schwartzberg, M.D., et al.
Poster Number: OT-06-01
Poster Category: Chemotherapy – Targeting Neutropenia
Poster Section: Ongoing Trial posters
Poster Presentation Date/Time: Wednesday, December 9, 2020: 8:00 AM CT

Copies of the posters will be available on the Spectrum Pharmaceuticals website following presentation at the meeting. ROLONTIS is an investigational drug not approved by the U.S. Food and Drug Administration (FDA) and the BLA is currently under review by the agency for the treatment of chemotherapy-induced neutropenia.

On December 4, 2020 Precision BioSciences, Inc. (Nasdaq: DTIL) a clinical stage biotechnology company dedicated to improving life with its novel and proprietary ARCUS genome editing platform, reported positive interim clinical results from its Phase 1/2a study of PBCAR0191, the Company’s off-the-shelf allogeneic CAR T cell therapy investigational candidate targeting CD19 (Press release, Precision Biosciences, DEC 4, 2020, View Source [SID1234572163]). As of the November 16, 2020 cutoff, 27 patients including 16 patients with aggressive NHL and 11 patients with aggressive B-ALL were enrolled and evaluated.

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"We’re very proud to share the latest update to our PBCAR0191 study. PBCAR0191, when combined with enhanced lymphodepletion resulted in a high objective response rate of 83% across enrolled NHL and B-ALL patients including those that previously received autologous CAR T therapy or stem cell transplants," said Matt Kane, CEO and Co-Founder of Precision BioSciences. "We believe that this data set represents an important and meaningful step forward in the development of allogeneic CAR T therapies and establishes Precision BioSciences as a leader in the field."

"I am extremely encouraged by what we have observed in this Phase I clinical trial of PBCAR0191. The data answered multiple questions associated with allogeneic cell therapies, including having seen no cases of GvHD. In the enhanced lymphodepletion arm, we observed the highest complete response rate seen to date in R/R aggressive NHL with an allogeneic product," said Bijal Shah, M.D., Associate Professor, Malignant Hematology Department, H. Lee Moffitt Cancer Center and Research Institute. "As a result, I am encouraged that the interim data from the PBCAR0191 Phase 1 trial is a meaningful step toward the goal of an off-the-shelf CAR T product that could help patients immediately, when they need it most."

Trial Design
Interim data from the Phase 1/2a study of PBCAR0191 includes data from 27 patients: 16 patients with R/R NHL and 11 patients with R/R B-ALL from multiple dose levels. In the NHL cohort, 100% of patients had aggressive lymphomas, 81% had stage III/IV disease, 63% had four or more courses of prior treatment and 25% had prior autologous CAR T. In the B-ALL cohort, 55% of patients had >20% blasts burden at baseline, 82% had 4+ courses of prior treatment and 45% had prior allogeneic stem cell transplant.

PBCAR0191 treatment at dose level (DL) 1 (3×105 cells), DL2 (1×106 cells), DL3 (3×106 cells) and split dose DL4 (2 doses at 3×106 cells) employed a single standard lymphodepletion (sLD) consisting of fludarabine (30 mg/m2/day for 3 days) plus cyclophosphamide (500 mg/m2/day for 3 days). PBCAR0191 was also dosed in an Enhanced Lymphodepletion Regimen consisting of PBCAR0191 cells at DL3 (n=5) or DL4 (n=1) plus fludarabine (30 mg/m2/day for 4 days) and cyclophosphamide (1000 mg/m2/day for 3 days).

For this study, in which patients received either sLD or eLD, response rates across R/R NHL and R/R B-ALL patient cohorts were as follows:

83% ORR at day 28 or later for patients across NHL (n=4) and B-ALL (n=2) who received PBCAR0191 when coupled with enhanced lymphodepletion.
At day 28 or later, 75% (3/4) of NHL patients who received PBCAR0191 with enhanced lymphodepletion achieved a CR. Meanwhile, 33% of NHL patients (n=9) across DL2 and DL3 using standard lymphodepletion achieved a CR.
The longest demonstrated response was > 11 months in a B-ALL patient at DL2.
Response Rates at Day ≥28 NHL (n=16) B-ALL (n=11)
ORR CR ORR CR
DL1 (3×105 cells) + sLD 67% (2/3) 0% (0/3) - -
DL2 (1×106 cells) + sLD 67% (2/3) 33% (1/3) 33% (1/3) 33% (1/3)
DL3 (3×106 cells) + sLD 50% (3/6) 33% (2/6) 25% (1/4) 25% (1/4)
DL4 (2 doses at 3×106 cells) + sLD - - 50% (1/2) 50% (1/2)
Enhanced LD Regimen 100% (4/4) 75% (3/4) 50% (1/2) 50% (1/2)
PBCAR0191, which incorporates Precision’s patented N6 co-stimulatory domain, demonstrated a clear dose dependent increase in peak cell expansion. Compared to sLD, eLD with PBCAR0191 at DL3 resulted in approximately 95-fold increase in peak cell expansion, and approximately 45-fold increase in area under the curve. This was associated with a higher complete response rate in NHL (75%).

Safety and Tolerability
In this dose escalation and dose expansion study, PBCAR0191 had an acceptable safety profile with no cases of GvHD, no cases of Grade ≥ 3 CRS, and no cases of Grade ≥ 3 ICANS.

One NHL patient who was treated with PBCAR0191 and eLD had previously received nine prior lines of therapy before entering the trial. The patient presented with persistent cytopenias at baseline and a history of infections, including bacterial sepsis. The patient had an episode of sepsis at day 27 which appeared to have resolved at day 33, following which a partial response was achieved at day 34. Unfortunately, the patient died at day 42 with grade 5 sepsis.

"We are rapidly leveraging learnings from this study and enrolling more patients into our enhance lymphodepletion regimen. In parallel, we continue to evaluate higher cell doses, repeat dosing and other novel methods to further optimize our dosing strategy," said Chris Heery, Chief Medical Officer at Precision BioSciences. "We also plan to pursue clinical development of PBCAR19B, our CD19 Stealth Cell candidate, which has shown to delay both T cell and natural killer cell mediated allogeneic rejection in vitro. We believe this is likely to result in improved persistence of allogeneic CAR T cells. We expect to move PBCAR19B into the clinic in 2021."

Company-Hosted Conference Call and Web Cast Information
Precision will host a conference call and webcast today, December 4, 2020 at 8:00 a.m. ET to discuss the updated interim clinical data and the learnings for PBCAR0191 from both the NHL and B-ALL cohorts of this trial, as well as PBCAR19B. The dial-in conference call numbers for domestic and international callers are (866) 996-7202 and (270) 215-9609, respectively. The conference ID number for the call is 6368255. Participants may access the live webcast and the accompanying presentation materials on Precision’s website View Source in the Investors and Media section under Events and Presentations. An archived replay of the webcast will be available on Precision’s website.

On December 4, 2020 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported an approved IND (Investigational new Drug) for the CD40 targeting antibody mitazalimab (Press release, Alligator Bioscience, DEC 4, 2020, View Source [SID1234572159]). IND approval by the US Food and Drug Administration (FDA) is a prerequisite to start clinical trials in the USA. Recently, new benchmark data was published showing that mitazalimab has the potential to be best-in-class in the CD40 field. The comparison demonstrated the potent immune-activating properties and anti-tumor effects of mitazalimab.

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"While the upcoming clinical Phase Ib/II study in pancreatic cancer, OPTIMIZE-1, will be starting in Europe, the IND opens up for later expansion in the US. This is essential for the future success of the product", said Per Norlén, CEO of Alligator Bioscience.", said Per Norlén, CEO of Alligator Bioscience. "Our key focus right now is to complete the submission of the CTA for start of OPTIMIZE-1 in the EU", he added.

The mitazalimab drug candidate has previously reported positive clinical data from a Phase I study performed by Janssen Biotech Inc., displaying a manageable safety profile as well as early signs of efficacy.

The information was submitted for publication, through the agency of the contact person set out above, at 9:00 a.m. CET on December 4, 2020.

On December 3, 2020 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that presentations on a series of abstracts highlighting updates on its in-house discovered lenvatinib mesylate (product name: LENVIMA, the orally available kinase inhibitor, "lenvatinib"), eribulin mesylate (product name: Halaven, halichondrin class microtubule dynamics inhibitor, "eribulin"), and H3B-6545 (selective estrogen alpha receptor covalent antagonist), discovered at Eisai’s U.S. research subsidiary H3 Biomedicine Inc., will be given at the 43rd San Antonio Breast Cancer Symposium (SABCS2020) Virtual Meeting, from December 8 to 11, 2020, in San Antonio, Texas in the United States (Press release, Eisai, DEC 3, 2020, View Source [SID1234574976]).

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At this symposium, regarding the combination therapy with lenvatinib and the anti-PD-1 therapy pembrolizumab (product name: KEYTRUDA) from Merck & Co., Inc., Kenilworth, N.J., U.S.A. (known as MSD outside of the United States and Canada), the results of the triple-negative breast cancer cohort in the basket-type Phase II clinical study (LEAP-005) for 6 types of previously treated, advanced solid tumors (Abstract No: PS12-07) is scheduled to be presented.

The results of analysis evaluating eribulin in the clinical practice in a subgroup of patients with metastatic breast cancer with a poor prognosis, in the United States, (Abstract No: PS13-37) will be published.

In addition, regarding H3B-6545, the results of evaluating tolerability, safety, and efficacy of Phase I/II clinical study for estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (Abstract No: PD8-06) and others will be presented.

In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib.

Eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. Eisai will continue to create innovation in the development of new drugs based on cutting-edge cancer research, as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

This release discusses investigational compounds and investigational uses for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational compounds or investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval

Major poster presentations at SABCS2020:
Product / Compound
Abstract No. Title / Scheduled Date and Time (local time: Central Standard Time)
Lenvatinib
PS12-07 Lenvatinib plus pembrolizumab for previously treated, advanced triple-negative breast cancer: Early results from the multicohort phase 2 LEAP-005 study
December 9 (Wed), 8:00 AM
Eribulin
PS13-37 Effectiveness of eribulin in poor prognosis subgroups of metastatic breast cancer (mBC) patients (Elderly, African Americans, and patients with liver metastases) in the United States
December 9 (Wed), 8:00 AM
H3B-6545
PD8-06 Phase I/II Trial of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer
December 10 (Thu), 2:15-3:30 PM
H3B-6545
PS12-15 Pharmacokinetics of H3B-6545 in Patients with Locally Advanced or Metastatic Estrogen Receptor-Positive HER2 Negative Breast Cancer
(ER+ and HER2- BC)
December 9 (Wed), 8:00 AM
H3B-6545
PS12-23 Development of H3B-6545, a first-in-class oral selective ER covalent antagonist (SERCA), for the treatment of ERaWT and ERaMUT breast cancer
December 9 (Wed), 8:00 AM