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OBI Pharma Granted FDA Orphan Drug Designation for the Treatment of Pancreatic Cancer for Its Antibody-Drug Conjugate (ADC) Targeted Cancer Therapy, OBI-999

On December 26, 2019 OBI Pharma, Inc., a Taiwan biopharma company (TPEx: 4174), reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for OBI-999 for the treatment of Pancreatic Cancer (Press release, OBI Pharma, DEC 26, 2019, View Source [SID1234552614]). OBI-999 is a first-in-class antibody drug conjugate targeting Globo H, a glycolipid antigen.

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A Phase 1/2 clinical trial of OBI-999 has commenced enrollment at the University of Texas M.D. Anderson Cancer Center, with Dr. Apostolia M. Tsimberidou as the Principal Investigator, in patients with locally advanced or metastatic solid tumors, including Pancreatic, Gastric, Colorectal and Esophageal Cancers (ClinicalTrials.gov Identifier: NCT04084366). The objective of the trial is to verify the safety and preliminary efficacy profile of OBI-999 in these patient populations.

Tillman Pearce, MD, CMO, OBI Pharma noted, "We are very excited about the potential value that OBI-999 may provide to patients with pancreatic cancer given both the high potency we have observed using OBI-999 in pancreatic cancer xenograft models and because many pancreas cancers highly overexpress Globo H, the glycolipid target of OBI-999, using the validated IHC assay that will be available for selecting patients for the Phase 2 portion of this first-in-human clinical trial."

About Pancreatic Cancer

Pancreatic Cancer originates in the exocrine or endocrine pancreatic cells and is thought to be caused by poor diet, smoking, and genetic factors. Pancreatic Cancer is a deadly disease that currently affects 69,839 people in the US and has a survival rate of only 8.5% at five years. In addition, treatment options are limited to surgical resection for patients with early stages of the disease and these patients may only have a five-year survival rate of up to 34.3%. As Pancreatic Cancer is asymptomatic in early stages, a majority of patients are undiagnosed or misdiagnosed until advanced stages of the disease. Surgery is no longer effective at this stage of the disease, leaving a large population with limited treatment options.

About Orphan Drug Designation (ODD)

The orphan drug designation provides OBI Pharma with potential benefits, including market exclusivity upon regulatory approval if received, exemption of FDA application fees, and tax credits for qualified clinical trials. The FDA’s Office of Orphan Drug Products grants orphan status to support development of medicines for rare diseases or conditions that affect fewer than 200,000 people in the U.S.

About OBI-999

OBI-999 is a novel first-in-class Antibody Drug Conjugate (ADC) with a proprietary linker technology that provides a consistent Drug-to-Antibody ratio (DAR) for cancer treatment that is based on Globo H, an antigen expressed in up to 15 epithelial cancers. OBI-999 uses a Globo H antibody to target cancer cells of high Globo H expression. By releasing a small molecule chemotherapeutic drug through the specificity of the antibody, it directly deploys cytotoxic therapy at the targeted cancer cells. OBI-999 is currently in a Phase 1/2 clinical trial (ClinicalTrials.gov Identifier: NCT04084366) to test its safety and efficacy as an oncology ADC therapy. In pre-clinical xenograft animal models in multiple tumor types (pancreatic, lung, gastric, and breast), OBI-999 has demonstrated profound tumor shrinkage at various doses. In pre-clinical single and repeated dose toxicology studies, OBI-999 was well-tolerated, and achieved a favorable safety margin which warrants further clinical development. OBI Pharma owns global rights to OBI-999.

Novocure to Participate in the 38th Annual J.P. Morgan Healthcare Conference

On December 26, 2019 Novocure (NASDAQ: NVCR) reported that it will participate in the 38th Annual J.P. Morgan Healthcare Conference on Monday, January 13, 2020, in San Francisco (Press release, NovoCure, DEC 26, 2019, View Source [SID1234552613]). William Doyle, Novocure’s Executive Chairman, will speak on behalf of the company and address questions from analysts. He is scheduled to present at 10 a.m. PST in the Elizabethan A/B conference room.

A live audio webcast of the presentation and all presentation materials can be accessed from the Investor Relations page of Novocure’s website, www.novocure.com/investor-relations/, and will be available for replay for at least 14 days following the event. Novocure has used, and intends to continue to use, its investor relations web page, as a means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD.

Spectrum Pharmaceuticals Provides Pipeline Update on Late Stage Programs

On December 26, 2019 Spectrum Pharmaceuticals, Inc. (NASDAQ-GS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported that its pre-specified primary endpoint in its Phase 2 clinical trial evaluating poziotinib in previously treated non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations was not met in Cohort 1 (Press release, Spectrum Pharmaceuticals, DEC 26, 2019, View Source [SID1234552612]). The company also announced that the Biologics License Application (BLA) for ROLONTIS(eflapegrastim) was accepted for review by the U.S. Food and Drug Administration (FDA) and set a Prescription Drug User Fee Act (PDUFA) date of October 24, 2020.

The ZENITH20 trial’s Cohort 1 enrolled a total of 115 patients who received 16 mg/day of poziotinib. The intent-to-treat analysis showed that 17 patients had a response (by RECIST) and 62 patients had stable disease for a 68.7% disease control rate (DCR). The confirmed objective response rate (ORR) was 14.8% (95% Confidence Interval (CI) 8.9%-22.6%). The median duration of response was 7.4 months. The safety profile was in-line with othersecond-generation EGFR tyrosine kinase inhibitors.

Joe Turgeon, President and CEO of Spectrum Pharmaceuticals said, "While the response rate of Cohort 1 in this trial was lower than we expected, the positive signals observed for this cohort provide support for the continued clinical evaluation of poziotinib in this patient population with significant unmet medical need. We look forward to providing read outs from Cohorts 2 and 3 in 2020, and plan to provide an update on the overall program strategy during the first quarter of 2020 after a full evaluation of the data from Cohort 1 is completed."

The ZENITH20 trial is made up of 7 independent cohorts. Cohorts 1 – 4 are each independently powered for a pre-specified statistical hypothesis with a primary endpoint of ORR. Cohorts 5 – 7 are exploratory studies. The futility analysis has been completed for Cohorts 2 and 3 which met their minimum threshold of responses to continue. The company expects to report results for these cohorts in 2020. Cohorts 4, 5, 6 and 7 are continuing per protocol.

"In Cohort 1, poziotinib has shown unequivocal biologic activity. Although we are disappointed by the ORR, we are highly encouraged by other measures including the disease control rate, the duration of response and the predictable safety profile," said Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. "A full review of Cohort 1 is underway and we plan to present the data at a future medical meeting."

The company also announced today that the FDA has accepted for review the BLA for ROLONTIS for the treatment of chemotherapy-induced neutropenia. The PDUFA target action date for the ROLONTIS BLA has been set for October 24, 2020.

"If approved, ROLONTIS could be the first novel granulocyte colony-stimulating factor (G-CSF) available to healthcare providers in over 15 years," said Joe Turgeon. "We have confidence in the future of ROLONTIS and are looking forward to potentially competing in this multibillion-dollar market."

The BLA for ROLONTIS is supported by data from two successful large pivotal Phase 3 clinical trials, ADVANCE (conducted under a SPA) and RECOVER. These trials evaluated the safety and efficacy of ROLONTIS in a total of 643 early-stage breast cancer patients for the treatment of neutropenia due to myelosuppressive chemotherapy. In both trials, ROLONTIS demonstrated the pre-specified hypothesis of non-inferiority (NI) in duration of severe neutropenia (DSN) and a similar safety profile to pegfilgrastim. ROLONTIS also demonstrated non-inferiority (NI) to pegfilgrastim in the DSN across all 4 cycles of chemotherapy (all NI p<0.0001) in both trials.

About Poziotinib

Poziotinib is a novel, oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR as well as HER2 and HER4. Importantly this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. Spectrum holds an exclusive license from Hanmi Pharmaceuticals to develop, manufacture, and commercialize poziotinib worldwide, excluding Korea and China. Poziotinib is currently being investigated by Spectrum and Hanmi in several mid-stage trials in multiple solid tumor indications.

About ROLONTIS and the ADVANCE and RECOVER Clinical Trials

The ROLONTIS ADVANCE trial was a Phase 3, multicenter, randomized, active-controlled, open label trial that enrolled 406 early-stage breast cancer patients, who received docetaxel and cyclophosphamide chemotherapy every 21 days for four cycles. Patients were randomized in a 1:1 ratio to receive eflapegrastim (n=196) or pegfilgrastim (n=210). The primary endpoint was the duration of severe neutropenia (DSN) in Cycle 1 of absolute neutrophil count [ANC] <0.5×109/L, as measured by ANC. Secondary endpoints included the DSN in Cycles 2, 3 and 4, time to ANC recovery, depth of ANC nadir and incidence of febrile neutropenia at Cycle 1. Patients with early stage breast cancer were treated on Day 1 of each of the four cycles with (adjuvant/neo-adjuvant) docetaxel and cyclophosphamide. On Day 2 of each cycle, patients received a single dose of either eflapegrastim or pegfilgrastim subcutaneously. The ADVANCE trial was conducted under a special protocol assessment (SPA) with the FDA.

The RECOVER trial was a Phase 3, multicenter, randomized, active-controlled, open label trial that enrolled 237 breast cancer patients who received docetaxel and cyclophosphamide chemotherapy every 21 days. Patients were randomized in a 1:1 ratio to receive eflapegrastim (n=118) or pegfilgrastim (n=119). The primary endpoint was the duration of severe neutropenia (DSN) in Cycle 1 of absolute neutrophil count [ANC] <0.5×109/L, as measured by ANC. Secondary endpoints included the DSN in Cycles 2, 3 and 4, time to ANC recovery, depth of ANC nadir and incidence of febrile neutropenia in Cycle 1. Patients with early stage breast cancer were treated on Day 1 of each of the four cycles with (adjuvant/neo-adjuvant) docetaxel and cyclophosphamide. On Day 2 of each cycle, patients received a single dose of either eflapegrastim or pegfilgrastim subcutaneously.

Immunomedics Announces FDA Acceptance for Filing of Biologics License Application Resubmission for Sacituzumab Govitecan to Treat Metastatic Triple-Negative Breast Cancer

On December 26, 2019 Immunomedics, Inc. (NASDAQ: IMMU) ("Immunomedics" or the "Company"), a leading biopharmaceutical company in the area of antibody-drug conjugates, reported that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company’s Biologics License Application (BLA) seeking accelerated approval of sacituzumab govitecan for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease, as a complete class 2 response (Press release, Immunomedics, DEC 26, 2019, View Source [SID1234552610]). The PDUFA target action date of the resubmitted BLA is June 2, 2020.

"We are pleased that the FDA has accepted our resubmission, which was a top priority for us in 2019," said Dr. Behzad Aghazadeh, executive chairman of Immunomedics. "We look forward to working closely with the FDA to facilitate their review of our BLA to enable us to bring this potentially transformational treatment to patients affected by mTNBC."

Sacituzumab govitecan has been awarded both Fast Track Designation and Breakthrough Therapy Designation by the FDA.

About Triple-Negative Breast Cancer (TNBC)

TNBC is an aggressive disease with an annual incidence estimated to be about 40,000 people, approximately 15% of all breast cancer types, in the United States alone. The incidence rate is higher among younger women and highest among non-Hispanic black and Hispanic women. TNBC tumors do not have sufficient estrogen, progesterone or HER2 receptor expression to indicate the use of hormonal or HER2-directed therapy. There is currently no standard-of-care chemotherapy for people with relapsed/refractory mTNBC. An overall response rate of about 10% and median progression-free survival of 2-3 months have recently been reported in late-stage mTNBC using single-agent chemotherapy.1,2

References

Cortés J, Lipatov O, Im S, et al. KEYNOTE-119: Phase 3 study of pembrolizumab (pembro) versus single-agent chemotherapy (chemo) for metastatic triple-negative breast cancer (mTNBC). Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

Kazmi, SM, Chatterjee D, Alexis K, et al. Real-World 1-Year Survival Analysis of Patients with Metastatic Breast Cancer with Liver or Lung Metastasis Treated with Eribulin, Gemcitabine or Capecitabine. Annals of Oncology (2019) 30 (suppl_5): v104-v142. 10.1093/annonc/mdz242
About Sacituzumab Govitecan

Sacituzumab govitecan, Immunomedics’ most advanced product candidate, is a novel, first-in-class ADC delivering SN-38, a potent topoisomerase I inhibitor, directly to tumor cells by targeting the Trop-2 antigen expressed by many solid cancers. It is currently under review by the U.S. Food and Drug Administration for accelerated approval as a treatment of patients with mTNBC who have received at least two prior therapies for metastatic disease. If approved, sacituzumab govitecan would be the first and only ADC approved for the treatment of mTNBC.

Astellas Strengthens Immuno-oncology Pipeline with Acquisition of Xyphos Biosciences, Inc.

On December 26, 2019 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Xyphos Biosciences, Inc. (CEO: James Knighton, "Xyphos") reported that Astellas has acquired Xyphos. With the acquisition Astellas will gain Xyphos’ novel and proprietary ACCEL (Advanced Cellular Control through Engineered Ligands) technology platform, as well as industry-leading immuno-oncology talent, to develop new and potentially better ways to mobilize, target and control immune cells to find, modulate and destroy targeted cells throughout the body (Press release, Astellas, DEC 26, 2019, View Source [SID1234552608]).

"At Astellas, immuno-oncology is a Primary Focus of our research and development strategy, and we are working on the development of next-generation cancer immuno-therapy using new modalities/technologies," said Kenji Yasukawa, President and CEO, Astellas. "The innovative technology in development at Xyphos fits perfectly in advancing our immuno-oncology strategy to create and deliver value for patients. Combining this technology with our capabilities in cell therapy that we have been working on so far, we can create next-generation high-function cells and maximize the value of our technology. We look forward to working with Xyphos’ superb team to advance and expand their clinical development programs to bring their novel therapeutics to patients."

Xyphos-Acquired

Xyphos-Acquired
"At Xyphos, we are driven to advance our innovative cell therapy technology platform as an exciting new approach to potentially manage and cure cancer," said James Knighton, Chief Executive Officer, Xyphos. "Astellas’ commitment to immuno-oncology makes them an ideal partner to advance our proprietary NKG2D-based NK-cell and T-cell platform to the next stage of clinical exploration. Further, we look forward to becoming part of Astellas to accelerate this immuno-oncology research and development in the vibrant South San Francisco community."

Xyphos has developed a flexible and versatile synthetic biology platform to direct cells of the immune system to target single or multiple tumor antigens while controlling the immune cell proliferation and endurance. Xyphos’s proprietary molecules can be delivered to natural immune cells or to engineered Chimeric Antigen Receptor (CAR) cells to generate immunotherapies for oncology. Xyphos’ patented CAR technology is based on an engineered modification to a natural human receptor named NKG2D. NKG2D exists on natural killer (NK) cells and some T-cells. The designed modification of NKG2D renders it inert, that is, unable to bind to any of its natural ligands, which occur on stressed cells. Through further protein engineering, several natural ligands of NKG2D have been modified to bind exclusively to the otherwise inert NKG2D receptor. Various functional molecules (for example, antibodies that recognize specific tumor antigens) are attached to the modified ligand. The ligand-directed functional molecules then bind exclusively to immune cells expressing the inert CAR on their surface – the proprietary convertibleCAR-cells. The CAR-cells can be directed by the ligand-bound antibody to seek, become activated and attacks a targeted cancer cell. Xyphos’ first convertibleCAR-T cell product candidate is in preclinical development and scheduled to be tested in a first-in-human clinical study in 2021.

Considering the acquisition, $ 120 million was paid upon closing of the acquisition, and Xyphos became a wholly owned subsidiary of Astellas. In addition to this payment and potential future development milestone payments, it will provide a total transaction value of $ 665 million.

The impact of this transaction on Astellas’ financial results in the fiscal year ending March 31, 2020 will be limited.