On March 11, 2021 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported the submission of a New Drug Application (NDA) to Japan’s Ministry of Health, Labour and Welfare (MHLW) for enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial cancer that has progressed after anti-cancer medication (Press release, Astellas Pharma, MAR 11, 2021, View Source [SID1234576468]). If approved, enfortumab vedotin would be the first antibody-drug conjugate (ADC) available in Japan for people living with this form of urothelial cancer.

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The submission is based on two global clinical trials with sites in Japan. The Phase 3 EV-301 trial evaluated enfortumab vedotin versus chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. The Phase 2 EV-201 trial evaluated enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy and who are ineligible for cisplatin (cohort 2).1,2

Enfortumab vedotin met the primary endpoints of overall survival (EV-301) and confirmed objective response rate per blinded independent central review (EV-201).3,4,5

"More than 24,000 people in Japan are diagnosed with urothelial cancer each year. For those whose cancer progresses despite treatment with chemotherapy and immunotherapy, there is no standard treatment option currently," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "Based on data from two global clinical trials, and following the Ministry of Health, Labour and Welfare’s review, enfortumab vedotin may offer a new option for these patients."

About Urothelial Cancer
Urothelial cancer is the most common type of bladder cancer (90 percent of cases), and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.6 Globally, approximately 549,000 new cases of bladder cancer and 200,000 deaths are reported annually.7 In Japan, it is estimated that 24,300 patients are diagnosed with this form of cancer and 9,500 deaths are reported annually.8

Locally advanced and metastatic urothelial cancer is an aggressive disease that is associated with poor survival and high healthcare costs.9 Five-year relative survival rates for metastatic disease are estimated to be approximately 7 percent.10

About the EV-301 Trial
The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician’s choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1 or PD-L1 inhibitor and platinum-based therapies.1 The primary endpoint is overall survival of participants treated with enfortumab vedotin compared to those treated with chemotherapy. Secondary endpoints include progression-free survival, duration of response, and overall response rate, as well as assessment of safety/tolerability and quality-of-life parameters. Results of the EV-301 trial were published in the New England Journal of Medicine.

About the EV-201 Trial
The EV-201 trial (NCT03219333) is a single-arm, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (cohort 2). The trial enrolled 128 patients in cohort 1 and 91 patients in cohort 2 at multiple centers internationally.2 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability. Results of the first cohort from the EV-201 trial were published in The Journal of Clinical Oncology and results from the second cohort were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancer Symposium.

About Enfortumab Vedotin
Enfortumab vedotin is an antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.11,12 Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).11

About the Astellas and Seagen Collaboration
Astellas and Seagen Inc. are co-developing enfortumab vedotin under a 50:50 worldwide development and commercialization collaboration. In the United States, Astellas and Seagen co-promote enfortumab vedotin under the brand name PADCEV (enfortumab vedotin-ejfv). In the Americas outside the US, Seagen holds responsibility for commercialization activities and regulatory filings. Outside of the Americas, Astellas holds responsibility for commercialization activities and regulatory filings.

On March 11, 2021 PhaseBio Pharmaceuticals, Inc. (Nasdaq: PHAS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapies for cardiopulmonary diseases, and BioVectra Inc., an innovative global contract development and manufacturing organization (CDMO), reported a commercial scale supply agreement for the production of bentracimab, PhaseBio’s lead product candidate currently in a global Phase 3 clinical trial (Press release, PhaseBio Pharmaceuticals, MAR 11, 2021, View Source [SID1234576484]). Bentracimab is a novel, human monoclonal antibody fragment that in earlier clinical trials has shown immediate and sustained reversal of the antiplatelet effects of Brilinta (ticagrelor).

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Under the terms of the agreement, BioVectra will provide its integrated CDMO services for the manufacturing of the active pharmaceutical ingredient (API) of bentracimab for use in PhaseBio’s ongoing global clinical trials and for global commercial use upon regulatory approval. Utilizing a cost-efficient, E.coli-based manufacturing process at its manufacturing site in Windsor, Nova Scotia, BioVectra recently completed the first GMP run of bentracimab at commercial scale. Going forward, PhaseBio plans to integrate API manufactured at commercial scale at BioVectra into the ongoing Phase 2b and Phase 3 REVERSE-IT clinical trials to support global regulatory filings.

"As we prepare for the next phase of growth for bentracimab, we’re pleased to sign this agreement with BioVectra for the commercial supply and development of our novel reversal agent," said Jonathan P. Mow, Chief Executive Officer of PhaseBio Pharmaceuticals. "Having recently expanded our global Phase 3 REVERSE-IT trial into Canada and the European Union, and with other countries on the horizon, the signing of this agreement and the completion of our first commercial-scale manufacturing run are important steps as we continue preparing our regulatory filings and commercialization efforts for bentracimab. We believe BioVectra will be an excellent partner as we move down the path of developing and potentially commercializing the first specific antiplatelet reversal agent for ticagrelor."

Pending approval of the drug by regulators, the partnership will enable PhaseBio to supply bentracimab at launch in the U.S. to key trauma and critical care centers. Based on data from IQVIA, PhaseBio believes that providing adequate bentracimab supply for initial stocking and demand-based reorders for these key centers will make bentracimab accessible to approximately 80% of the population in the U.S. who are prescribed P2Y12 inhibitors like ticagrelor.

"We’re excited to be partnering with PhaseBio under this new commercial agreement for the high-volume scale-up and global supply of bentracimab," said Oliver Technow, Chief Executive Officer of BioVectra. "BioVectra is an expert CDMO with proven, specialized capability in scaling the most complex biologic drug substances produced from fermentation. Leveraging our fully integrated approach and 50 years of experience, our highly-skilled team looks forward to continuing to make a difference in patients’ lives by delivering on and supporting PhaseBio’s global commercialization of bentracimab from our new, large-scale Microbial Biomanufacturing facility."

About Bentracimab (PB2452)

Bentracimab is a novel, recombinant, human monoclonal antibody antigen-binding fragment designed to reverse the antiplatelet activity of ticagrelor in major bleeding and urgent surgery situations. In a Phase 1 clinical trial, bentracimab demonstrated the potential to bring life-saving therapeutic benefit through immediate and sustained reversal of ticagrelor’s antiplatelet activity, mitigating concerns regarding bleeding risks associated with the use of antiplatelet drugs. The Phase 1 clinical trial of bentracimab in healthy volunteers was published in the New England Journal of Medicine in March 2019. In April 2019, bentracimab received Breakthrough Therapy Designation from the FDA. Breakthrough Therapy Designation may be granted by the FDA when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapy. In September 2019, PhaseBio completed a Phase 2a trial in which bentracimab was investigated in older and elderly subjects on dual antiplatelet therapy of ticagrelor and low-dose aspirin. Additionally, the Phase 2a trial investigated a bentracimab regimen for the reversal of supratherapeutic doses of ticagrelor in healthy younger subjects. In both arms of the trial, bentracimab achieved immediate and sustained reversal of the antiplatelet effects of ticagrelor and was generally well-tolerated, with only minor adverse events reported. These results are consistent with the results observed in healthy younger subjects treated with ticagrelor in the previously published Phase 1 trial. PhaseBio initiated the REVERSE-IT trial, a pivotal Phase 3 clinical trial of bentracimab, in March 2020 to support a Biologics License Application for bentracimab in both major bleeding and urgent surgery indications. There are currently no approved reversal agents for ticagrelor or any other antiplatelet drugs.

On March 11, 2021 Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer, reported financial results for the fourth quarter and year ended December 31, 2020, and highlighted recent corporate accomplishments (Press release, Galera Therapeutics, MAR 11, 2021, View Source [SID1234576507]).

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"In 2020, Galera presented positive interim data demonstrating that our dismutase mimetics have the potential to benefit the anti-cancer side of the therapeutic index of radiotherapy," said Mel Sorensen, M.D., President and CEO of Galera. "This encouraging interim data from our pilot placebo-controlled Phase 1/2 trial in patients with pancreatic cancer was presented at ASTRO in late 2020. We look forward to providing the final data readout from this trial in the second half of 2021 and advancing this regimen with the initiation of our Phase 2b GRECO-2 trial of GC4711 in combination with SBRT in patients with LAPC in the first half of 2021."

Dr. Sorensen continued, "We are excited for the year ahead, which we believe will be transformative for our company, with the topline data readout of our Phase 3 ROMAN trial. In anticipation, we continue our preparations for the commercial launch of avasopasem manganese."

Recent Corporate Highlights

Severe Oral Mucositis (SOM)

Continued enrollment in the Phase 3 ROMAN trial of avasopasem for the treatment of SOM in patients with locally advanced head and neck cancer (HNC) undergoing standard-of-care radiotherapy. The Company remains on track to complete enrollment in the first half of 2021 and report topline data in the second half of 2021.
Completed enrollment in the Phase 2a EUSOM multi-center trial in Europe assessing the safety of avasopasem in patients with HNC undergoing standard-of-care radiotherapy. The Company remains on track to report topline data in the second half of 2021.
Locally Advanced Pancreatic Cancer (LAPC)

Presented positive interim data from the pilot placebo-controlled Phase 1/2 anti-cancer trial of avasopasem in combination with SBRT in patients with LAPC at the American Society for Radiation Oncology (ASTRO) virtual Annual Meeting in late 2020. Data on all patients through a minimum follow-up of three months demonstrated better tumor outcomes, including overall survival, with avasopasem compared to placebo. The Company plans to provide final data from this trial with at least one year of follow-up data on all patients in the second half of 2021.
Remain on track to initiate the Phase 2b GRECO-2 trial of GC4711, Galera’s second superoxide dismutase mimetic candidate, in combination with SBRT in patients with LAPC in the first half of 2021. GRECO-2 is a randomized, double-blind, placebo-controlled trial to evaluate the effect of 100 mg of GC4711 versus placebo in combination with SBRT on overall survival in patients with LAPC. The trial is expected to enroll approximately 160 patients.
Non-Small Cell Lung Cancer (NSCLC)

Continued enrollment in the Phase 1/2 GRECO-1 trial of GC4711 in combination with SBRT in patients with NSCLC. The Phase 2 portion of GRECO-1 is randomized, double-blind, and placebo-controlled to evaluate the effect of 100 mg of GC4711 versus placebo. The Company continues to expect to report initial data in the first half of 2022.
Esophagitis

Continued enrollment in the Phase 2a AESOP trial of avasopasem evaluating its ability to reduce the incidence of esophagitis induced by radiotherapy in patients with lung cancer. The Company remains on track to report topline data in the first half of 2022.
Fourth Quarter 2020 Financial Highlights

Research and development expenses were $14.6 million in the fourth quarter of 2020, compared to $13.3 million for the same period in 2019. The increase was primarily attributable to avasopasem and GC4711 development costs, as well as higher employee-related costs due to increased headcount and share-based compensation expense. The increases were partially offset by decreased avasopasem and GC4711 preclinical spend.

General and administrative expenses were $4.3 million in the fourth quarter of 2020, compared to $2.9 million for the same period in 2019. The increase was primarily the result of employee-related costs from increased headcount and share-based compensation expense, and increased insurance, professional fees and other operating costs as a result of becoming a public company.

Galera reported a net loss of $(20.1) million, or $(0.80) per share, for the fourth quarter of 2020, compared to a net loss of $(16.7) million, or $(1.31) per share, for the same period in 2019.

As of December 31, 2020, Galera had cash, cash equivalents and short-term investments of $72.8 million. Galera expects that its existing cash, cash equivalents and short-term investments, together with the expected payments from Blackstone in the amount of $57.5 million upon the achievement of certain clinical enrollment milestones in the ROMAN trial and the anti-cancer program in combination with SBRT under the amended royalty agreement, will enable Galera to fund its operating expenses and capital expenditure requirements into the second half of 2022. We expect to achieve these clinical enrollment milestones in the first half of 2021.
Full Year 2020 Financial Highlights

Research and development expenses were $54.8 million for the year ended December 31, 2020, compared to $42.3 million for the year ended December 31, 2019. The increase was primarily attributable to avasopasem development costs due to increased expenses in the Phase 3 ROMAN trial, additional clinical trials including the Phase 2a AESOP trial and the Phase 2a EUSOM trial, and manufacturing scale-up activities. In addition, employee-related costs also increased due to increased headcount and share-based compensation expense.
General and administrative expenses were $15.7 million for the year ended December 31, 2020, compared to $8.4 million for the year ended December 31, 2019. The increase was primarily the result of employee-related costs from increased headcount and share-based compensation expense, and increased insurance, professional fees and other operating costs as a result of becoming a public company.
Galera reported a net loss of $(74.2) million, or $(2.98) per share, for the year ended December 31, 2020, compared to a net loss of $(51.9) million, or $(16.31) per share, for the year ended December 31, 2019.

On March 11, 2021 AVEO Oncology (Nasdaq: AVEO) reported that it has completed a drawdown of $20 million under its previously announced $45 million loan and security agreement with Hercules Capital, Inc. (NYSE: HTGC, "Hercules") and its affiliates (Press release, AVEO, MAR 11, 2021, View Source [SID1234576543]). This second tranche was made available in connection with the recent U.S. Food and Drug Administration (FDA) approval of FOTIVDA (tivozanib).

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"With the additional $20 million now available to us from Hercules, AVEO is well positioned to support what we believe will be a successful launch of FOTIVDA in the U.S.," said Michael Bailey, president and chief executive officer of AVEO. "Our core infrastructure and core commercial organization is in place, and we now look forward to delivering on the promise of FOTIVDA. We also expect to see meaningful progress within our pipeline programs in the coming quarters, including our immunotherapy combination programs for tivozanib, our Phase 2 study of ficlatuzumab and our recently initiated Phase 1 study of AV-380."

With the closing of the second tranche, AVEO has drawn down a total of $35 million under its loan and security agreement with Hercules. The loan facility has a maturity date of September 1, 2023, extendable to September 1, 2024, and an interest-only period through September 30, 2021, extendable to September 30, 2022, in each case upon the achievement of certain performance milestones related to the commercialization of FOTIVDA. An additional $5 million tranche becomes available if net product revenues of FOTIVDA reach $20 million within a specified time frame, and the final $5 million tranche would be available after that time upon the lender’s consent.

As previously disclosed, AVEO believes that its $68.8 million in cash, cash equivalents and marketable securities as of September 30, 2020, along with proceeds from the $20 million loan facility drawdown, together with anticipated partnership cost sharing reimbursements, royalties from EUSA’s FOTIVDA sales and the resulting product revenues upon the commercial launch of FOTIVDA (tivozanib) in the U.S. and the potential additional $10 million in credit under the Hercules loan, would allow the Company to fund planned operations into 2022.

On March 11, 2021 BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV), reported the publication of proof-of-concept data on a novel, fully human FcγRIIB-blocking antibody, BI-1607, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, being held virtually April 10-15 and May 17-21 (Press release, BioInvent, MAR 11, 2021, View Source,c3303983 [SID1234576469]).

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"The data on BI-1607 are very exciting and provide proof-of-concept of its ability to enhance anti-cancer immunity, illustrated by its ability to boost activity and overcome resistance to CTLA-4-based therapy," said Martin Welschof, CEO of BioInvent. "We are looking forward to advancing BI-1607 into clinical development and expect to submit a clinical trial application during H2 2021. It will be BioInvent’s fourth drug candidate in clinical development, further demonstrating the strength and productivity of our technology platform."

Understanding mechanisms and overcoming resistance to distinct classes of antibody drugs has the potential to further improve cancer outcomes, explains the AACR (Free AACR Whitepaper) abstract, entitled "A novel FcγRIIB-blocking antibody to enhance FcγR-dependent antitumor immunity". BI-1607 has a novel mechanism-of-action and is designed to enhance FcγR-dependent antitumor immunity. The abstract outlines how BI-1607 enhances the therapeutic activity of anti-CTLA-4 in responsive (MC38) or resistant (CT26) experimental disease models (syngeneic immune competent) and that a triple combination – of BI-1607, anti-PD-1 and low dose anti-CTLA-4 – significantly enhanced survival in a B16 tumor model not responsive to checkpoint blockade. For further information and access to the full abstract, visit View Source!/9325/presentation/2743.

BioInvent’s lead compound BI-1206, evaluated in two separate Phase I trials for hematological or solid tumors, is one of three ongoing drug candidates in clinical development. The company initiated a Phase I/IIa trial of anti-TNFR2 antibody BI-1808 in January 2021 and a Phase l/lla trial of the novel oncolytic vaccinia virus BT-001, together with partner Transgene, in March 2021.