On March 4, 2022 CASI Pharmaceuticals, Inc. (Nasdaq: CASI), a U.S. biopharmaceutical company focused on developing and commercializing innovative therapeutics and pharmaceutical products, reported, that the Company has entered into a renewal exclusive distribution agreement, whereby under the terms of the agreement, China Resources Pharmaceutical Commercial Group International Trading Co., Ltd. (CRPCGIT), previously called "China Resources Guokang Pharmaceuticals Co., Ltd. (CRGK)", will continue to be the sole distributor for the sale of EVOMELA (melphalan) for Injection in China (Press release, CASI Pharmaceuticals, MAR 4, 2022, View Source [SID1234609520]).

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Larry Zhang, CASI’s Global President, commented, "EVOMELA has shown rapid revenue growth in the past three years and reached $30 million in 2021. In combination with the efforts of all CASI employees, cooperation with CRPCGIT has been tremendously valuable in achieving long-term growth. CRPCGIT provides reliable and efficient distribution services that significantly increase accessibility to EVOMELA for physicians and patients. We look forward to our future collaboration."

On March 4, 2022 bluebird bio, Inc. (NASDAQ: BLUE) ("bluebird bio" or the "Company") reported financial results and business highlights for the fourth quarter and full year ended December 31, 2021, shared recent operational progress, and provided a corporate update (Press release, bluebird bio, MAR 4, 2022, View Source [SID1234609519]).

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"2022 is set up to be a landmark year for bluebird bio, with LVV gene therapies for β-thalassemia and cerebral adrenoleukodystrophy under review by the U.S. Food and Drug Administration (FDA) and plans to submit a Biologics License Application (BLA) for lovo-cel for sickle cell disease (SCD) early next year," said Andrew Obenshain, CEO, bluebird bio. "Underscoring these significant milestones is a continued focus on commercialization and financial discipline to enable the delivery of these transformative therapies to patients and their families."

RECENT HIGHLIGHTS

LOVO-CEL

UPDATE ON PARTIAL CLINICAL HOLD FOR PATIENTS UNDER THE AGE OF 18 – Today, bluebird bio provided an update on the FDA’s partial clinical hold for the lovotibeglogene autotemcel (lovo-cel) gene therapy clinical program for patients under the age of 18 with SCD. As previously communicated, in January 2022, bluebird bio received questions from the FDA related to the partial clinical hold. Following review of the questions from the FDA and an assessment of the timeline for manufacturing drug product lots and collecting analytical comparability data in the HGB-210 study, bluebird bio is reaffirming plans to submit the BLA for lovo-cel in Q1 2023. The Company continues to work with regulators to resume treating patients under the age of 18. In the meantime, the Company is collecting comparability data from drug product lots manufactured for adult patients in the HGB-210 study. As previously communicated, bluebird bio has treated all patients in HGB-206 Group C who will form the primary basis of efficacy for BLA submission, with the demonstration of analytical comparability and validation of the Company’s commercial manufacturing process as the key remaining actions prior to submission of the planned BLA.
HGB-206 FINAL INFUSION – Today, bluebird bio announced the completion of the final patient infusion in the HGB-206 study, the ongoing Phase 1/2 open-label study designed to evaluate the efficacy and safety of lovo-cel for sickle cell disease. A total of 45 patients have been treated with lovo-cel in the HGB-206 study across three treatment cohorts: Groups A (n=7), B (n=2) and C (n=36).
DATA AT ASH (Free ASH Whitepaper) AND PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE – On December 12, 2021, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, bluebird bio presented new data showing a complete elimination of severe vaso-occlusive events (VOEs) through up to 36 months of follow-up in 25 patients who had a history of at least four severe VOEs and at least six months follow-up in Group C of its ongoing Phase 1/2 HGB-206 study of lovo-cel for patients with SCD. The safety data presented remain consistent with the known side effects of autologous hematopoietic stem cell collection, myeloablative single-agent busulfan conditioning and underlying SCD. Select data from the Group C cohort of the HGB-206 study were simultaneously published in The New England Journal of Medicine (NEJM).
BETI-CEL

BETI-CEL BLA ACCEPTANCE AND PRIORITY REVIEW – On November 22, 2021, bluebird bio announced that the FDA accepted for priority review its BLA for betibeglogene autotemcel (beti-cel), the Company’s potentially curative gene therapy for adult, adolescent and pediatric patients with β-thalassemia across all genotypes who require regular red blood cell (RBC) transfusions. On January 18, 2022, the FDA extended the review period for the BLA and revised the Prescription Drug User Fee Act (PDUFA) goal date to August 19, 2022. Under priority review, bluebird would be eligible to receive a priority review voucher upon potential approval of beti-cel in 2022.
DATA AT ASH (Free ASH Whitepaper) AND PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE – On December 11, 2021, at the 63rd ASH (Free ASH Whitepaper) Annual Meeting, bluebird bio presented new data showing that adult and pediatric patients living with β-thalassemia who require regular RBC transfusions can produce normal or near-normal levels of total hemoglobin and continue to remain transfusion-free, and achieve stable iron markers, through up to seven years of follow-up in the ongoing long-term follow-up study (LTF-303) of beti-cel. In the safety data presented there were zero deaths or vector-derived replication-competent lentivirus, and no events of insertional oncogenesis or malignancy in LTF-303. The majority of AEs and SAEs were unrelated to beti-cel and consistent with the known side effects of HSC collection and busulfan conditioning regimen. Data from the pivotal HGB-207 Northstar-2 study were also simultaneously published in an original article in the NEJM.
ELI-CEL

ELI-CEL CLINICAL HOLD – The Company remains in communication with the FDA regarding the clinical hold. The FDA has notified the Company that the clinical hold on the elivaldogene autotemcel (eli-cel) program will remain in place and requested additional information about safety events and monitoring in the eli-cel clinical program.
ELI-CEL BLA ACCEPTANCE AND PRIORITY REVIEW – On December 17, 2021, bluebird bio announced that the FDA accepted for priority review its BLA for eli-cel, the Company’s gene therapy for cerebral adrenoleukodystrophy in patients less than 18 years of age. On January 18, 2022, the FDA extended the review period for the BLA and revised the PDUFA goal date to September 16, 2022. Under priority review, bluebird would be eligible to receive a priority review voucher upon potential approval of eli-cel in 2022.
COMPANY

NEW BOARD OF DIRECTORS APPOINTMENT – Today, bluebird bio announced the appointment of Charlotte Jones-Burton, M.D., M.S., to its Board of Directors. Dr. Jones-Burton is Senior Vice President, Product Development and Strategy at Chinook Therapeutics, a clinical-stage biotechnology company discovering, developing and commercializing precision medicines for rare, severe chronic kidney diseases. With more than 20 years of experience as a clinical development leader, internal medicine and nephrology physician and academician, Dr. Jones-Burton is dedicated to creating healthier communities through drug development, patient advocacy and people engagement. Dr. Jones-Burton earned a medical degree and Master of Science degree in Epidemiology and Preventive Medicine, with a concentration in Clinical Research, from the University of Maryland School of Medicine. Her postgraduate training included an internal medicine residency and a nephrology fellowship at the University of Maryland Medical Systems.
UPCOMING ANTICIPATED MILESTONES

LOVO-CEL

The Company is in active communication with the FDA to resolve the partial clinical hold and resume treating patients under the age of 18.
The Company plans to complete manufacturing of commercial drug product validation lots by mid-2022.
The Company expects to confirm vector and drug product analytical comparability by Q4 2022.
The Company is on track to submit its BLA for lovo-cel in Q1 2023.
BETI-CEL

The FDA has set a PDUFA goal date of August 19, 2022, for a decision on the approval of beti-cel in patients with β-thalassemia with commercial launch expected to follow in mid-2022 if approved.
bluebird bio anticipates an FDA advisory committee meeting for beti-cel and eli-cel will be held over the course of two days on June 9-10, 2022.
ELI-CEL

The FDA has set a PDUFA goal date of September 16, 2022, for a decision on the approval of eli-cel in patients with cerebral adrenoleukodystrophy with commercial launch expected to follow by the end of 2022 if approved.
bluebird bio anticipates an FDA advisory committee meeting for beti-cel and eli-cel will be held over the course of two days on June 9-10, 2022.
FOURTH QUARTER AND FULL YEAR 2021 FINANCIAL RESULTS

Cash Position: The Company’s restricted cash, cash and cash equivalents and marketable securities balance was approximately $442 million, including restricted cash of approximately $46 million, as of December 31, 2021. The full-year 2022 cash burn is expected to be less than $400 million. The Company’s expectation to generate operating losses and negative operating cash flows in the future and the need for additional funding to support its planned operations raise substantial doubt regarding its ability to continue as a going concern for a period of one year after the date that its consolidated financial statements for the year ended December 31, 2021 are issued.

The Company is exploring multiple financing opportunities, including plans for the sale of priority review vouchers, which the Company would be eligible to receive upon potential approval of beti-cel and eli-cel in 2022, while focusing on further cost efficiencies.

Revenues: Total revenue from continuing operations was $1.6 million and $3.7 million for the three and twelve months ended December 31, 2021, respectively. The Company did not recognize revenue from continuing operations in 2020.

R&D Expenses: Research and development expenses from continuing operations were $79.4 million for the three months ended December 31, 2021, compared to $58.8 million for the three months ended December 31, 2020. Research and development expenses were $319.9 million for the twelve months ended December 31, 2021, compared to $319.3 million for the twelve months ended December 31, 2020.

SG&A Expenses: Selling, general and administrative expenses from continuing operations were $53.2 million for the three months ended December 31, 2021, compared to $80.6 million for the three months ended December 31, 2020. Selling, general and administrative expenses were $210.0 million for the twelve months ended December 31, 2021, compared to $240.0 million for the twelve months ended December 31, 2020.

Net Loss: Net loss from continuing operations was $132.3 million for the three months ended December 31, 2021, compared to $136.3 million for the three months ended December 31, 2020. Net loss from continuing operations was $562.6 million for the twelve months ended December 31, 2021, compared to $561.1 million for the twelve months ended December 31, 2020.

On March 4, 2022 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported that it will participate in two upcoming virtual investor conferences (Press release, Arvinas, MAR 4, 2022, View Source [SID1234609518]):

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Cowen & Co. 42nd Annual Health Care Conference on Monday, March 7. Ian Taylor, Ph.D., Chief Scientific Officer, will participate in a fireside chat. A live audio webcast of the presentation will be available here and on the Events + Presentations section of the Company’s website.

Guggenheim Targeted Protein Degradation Day on Wednesday, March 16. Ian Taylor, Ph.D., Chief Scientific Officer, will participate in a fireside chat. A live audio webcast of the presentation will be available here and on the Events + Presentations section of the Company’s website.

On March 4, 2022 Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS) and Shanghai Junshi Biosciences Co., Ltd ("Junshi Biosciences", HKEX: 1877; SSE: 688180) reported the online publication in Cancer Cell of Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): a multi-center randomized phase 3 trial (Press release, Coherus Biosciences, MAR 4, 2022, View Source [SID1234609514]). The manuscript publication was accompanied by a Cancer Cell editorial preview entitled Jupiter-06 establishes immune checkpoint inhibitors as essential first-line drugs for the treatment of advanced esophageal squamous cell carcinoma.

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JUPITER-06 achieved the co-primary endpoints of progression free survival ("PFS") and overall survival ("OS") with statistically significant and clinically meaningful improvements for patients treated with the toripalimab and chemotherapy combination compared to chemotherapy alone. The study results were first presented in a mini-oral session during the European Society for Medical Oncology ("ESMO") Congress 2021.

"The clinically meaningful results of JUPITER-06, as published in this internationally recognized, peer-reviewed journal, demonstrate toripalimab’s ability to deliver significant benefits to patients receiving first-line treatment of advanced or metastatic esophageal squamous cell carcinoma," said Dr. Patricia Keegan, Chief Medical Officer of Junshi Biosciences.

"Toripalimab interacts with PD-1 through a differentiated domain on the PD-1 surface, the FG loop, and has strong receptor internalization upon binding, resulting in a consistent reduction of PD-1 from the T-cell surface. We have hypothesized that this unique feature could enable a more robust response to antigen stimulation, and in our clinical trials, including JUPITER-06, we are closely monitoring PD-L1 expression as well as clinical efficacy in both PD-L1 high and PD-L1 low patient populations," commented Dr. Sheng Yao, Senior Vice President of Junshi Biosciences.

"The robust results from the JUPITER-06 study add to the emerging body of clinical evidence of toripalimab’s clinical activity across multiple tumor types. Importantly, ESCC patients with low PD-L1 expression represent a high unmet need, and we are encouraged by these results in patients with ESCC and the potential of toripalimab plus chemotherapy to offer improved clinical outcomes for these patients," said Denny Lanfear, CEO of Coherus. "We are working closely with our partners at Junshi Biosciences to make toripalimab and additional complementary immuno-oncology agents available to patients in the U.S. as part of our mission to advance patient care and outcomes in oncology."

Highlights from the peer-reviewed manuscript are summarized below. A total of 514 treatment-naive advanced or metastatic patients were randomized (1:1) to receive toripalimab in combination with paclitaxel plus cisplatin ("TP") chemotherapy (the "toripalimab arm") or placebo in combination with TP chemotherapy (the "placebo arm"), followed by toripalimab or placebo maintenance. The co-primary endpoints were PFS as assessed by a blinded independent central review ("BICR") and OS.

A statistically significant improvement in OS was detected in the toripalimab arm:
Median OS in the toripalimab and placebo arms were 17 vs. 11 months respectively. An interim analysis of OS revealed that, by the cutoff date of March 22, 2021, there were 70 deaths in the toripalimab arm (27.2%) vs. 103 deaths in the placebo arm (40.1%) (hazard ratio ("HR") = 0.58; 95% confidence interval ("CI"), 0.43-0.78; P=0.0004).
One-year OS rates were 66.0% vs. 43.7% for the toripalimab arm vs. the placebo arm, respectively.
A statistically significant improvement in PFS was detected in the toripalimab arm:
Median PFS in the toripalimab arm and placebo arm were 5.7 vs 5.5 months, respectively, (HR = 0.58; 95% CI, 0.46–0.74; P<0.0001).
One-year PFS rates were 27.8% vs. 6.1% for the toripalimab arm vs. the placebo arm, respectively.
Treatment effects generally favored the toripalimab arm across subgroup analyses, including among patients with low/negative PD-L1 tumor expression (PD-L1 CPS<1):
The OS and PFS benefits were observed across key subgroups, including all PD-L1 expression subgroups. Specifically, the HRs for PFS between the toripalimab and placebo arms were 0.58 (95% CI, 0.44-0.75), 0.66 (95% CI, 0.37-1.19), and 0.56 (95% CI, 0.41-0.78) in the PD-L1 CPS ≥ 1, CPS < 1, and CPS<10 subgroups respectively. The HRs for OS between the toripalimab and placebo arms were 0.61 (95% CI, 0.44-0.87), 0.61 (95% CI, 0.30-1.25), and 0.61 (95% CI, 0.40-0.93) in the CPS ≥ 1, CPS < 1, and CPS<10 subgroups respectively. The Combined Positive Score ("CPS") equals the total number of PD-L1 staining cells (tumor cells and immune cells) divided by the total number of viable tumor cells, multiplied by 100.
The addition of toripalimab to TP did not lead to an unacceptable increase in toxicity:
Incidence of grade >3 treatment emergent adverse events ("TEAEs") was similar between the two arms. By the cutoff date, 99.2% of patients in each arm experienced at least one TEAE. Of those, 8.2% in each arm were fatal, though only 0.4% (toripalimab) and 1.2% (placebo) were deemed to be related to treatment. No new safety signals were observed.
Junshi Biosciences and Coherus are evaluating the potential to register toripalimab in combination with platinum-based chemotherapy for the first-line treatment of advanced or metastatic ESCC in the United States. In late 2021, the United States Food and Drug Administration ("FDA") granted Orphan Drug Designation ("ODD") for toripalimab for the treatment of esophageal cancer. In China, the supplemental New Drug Application for this indication was accepted in July 2021 by the National Medical Products Administration ("NMPA").

About JUPITER-06

The JUPITER-06 Study (ClinicalTrials.gov identifier: NCT03829969) is a multi-center, randomized, double-blind, placebo-controlled Phase 3 clinical trial comparing the efficacy and safety of toripalimab versus placebo in combination with TP as a first-line treatment for patients with advanced or metastatic ESCC. Between January 28, 2019 and November 30, 2020, 514 treatment-naïve advanced or metastatic ESCC patients from 72 centers across China were randomized (1:1) to receive toripalimab or placebo plus TP followed by toripalimab or placebo maintenance. The co-primary endpoints were PFS, defined as the time from randomization to the first documented disease progression or death from any cause assessed by BICR per RECIST v1.1; and OS, defined as the time from randomization to death from any cause. Secondary endpoints included PFS assessed by the investigator, PFS in the per-protocol population, objective response rate ("ORR"), duration of response ("DoR"), disease control rate ("DCR"), PFS and OS rates at 1-year and 2-year, and safety. Both arms received a median of 6 cycles of TP, and a median of 7 cycles of either toripalimab or placebo. By the cutoff date, 91 (35.4%) patients in the toripalimab arm and 69 (26.8%) patients in the placebo arm remained on the study treatment. Professor Ruihua Xu, from Sun Yat-sen University Cancer Center, is the principal investigator for this study.

About Toripalimab
Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 promote the immune system’s ability to attack and kill tumor cells.
More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally by Junshi Biosciences, including in China, the United States, Southeast Asia, and European countries. Ongoing or completed pivotal clinical trials evaluating the safety and efficacy of toripalimab cover a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin.
In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI). Currently, there are four approved indications for toripalimab in China:

unresectable or metastatic melanoma after failure of standard systemic therapy;
recurrent or metastatic nasopharyngeal carcinoma ("NPC") after failure of at least two lines of prior systemic therapy;
locally advanced or metastatic urothelial carcinoma that failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy;
in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic NPC.
The first three indications have been included in the National Reimbursement Drug List ("NRDL") (2021 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for melanoma and NPC.

In addition, two supplemental New Drug Applications ("NDAs") for toripalimab are currently under review by the National Medical Products Administration ("NMPA") in China:

in combination with chemotherapy as the first-line treatment of patients with advanced or metastatic ESCC.
in combination with chemotherapy as the first-line treatment of patients with advanced or metastatic non-small cell lung cancer ("NSCLC") with no EGFR or ALK sensitizing mutations.
In the United States, the FDA has granted priority review for the toripalimab biologics license application ("BLA") for the treatment of recurrent or metastatic NPC, an aggressive head and neck tumor which has no FDA-approved immuno-oncology treatment options. The FDA has assigned a Prescription Drug User Fee Act ("PDUFA") target action date for April 2022 for the toripalimab BLA. The FDA granted Breakthrough Therapy designation for toripalimab in combination with chemotherapy for the first-line treatment of recurrent or metastatic NPC in 2021 as well as for toripalimab monotherapy in the second or third-line treatment of recurrent or metastatic NPC in 2020. Additionally, the FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and orphan drug designation for the treatment of esophageal cancer, NPC, mucosal melanoma and soft tissue sarcoma. In 2021, Coherus in-licensed rights to develop and commercialize toripalimab in the United States and Canada. Coherus and Junshi Biosciences plan to file additional toripalimab BLAs with the FDA over the next three years for multiple other cancer types.

On March 4, 2022 PharmaMar (MSE:PHM) reported the receipt of payment of $25 million (€22 million) from its U.S. partner, Jazz Pharmaceuticals, after reaching the first commercial milestone, set out in its license agreement in relation to 2021 sales (Press release, PharmaMar, MAR 4, 2022, https://pharmamar.com/en/pharmamar-receives-the-first-commercial-milestone-payment-from-jazz-pharmaceuticals-for-us25-million/ [SID1234609510]).

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After a successful launch of Zepzelca (lurbinectedin) in the United States by Jazz Pharmaceuticals, lurbinectedin is established as the treatment of choice in second-line SCLC. The sales achieved in 2021 have resulted in the first commercial milestone payment.

Lurbinectedin received accelerated approval for the second-line treatment of SCLC in June 2020 in the United States.

Following the recent $25 million payment, PharmaMar is eligible for additional regulatory milestone payments of up to $153 million and additional commercial milestone payments of up to $528 million related to achieving certain milestones in the U.S. and Canada.