On January 22, 2024 YS Biopharma Co., Ltd. (NASDAQ: YS) ("YS Biopharma") along with its subsidiaries ("YS Group" or the "Company"), a global biopharmaceutical company dedicated to discovering, developing, manufacturing, and delivering new generations of vaccines and therapeutic biologics for infectious diseases and cancer, reported its unaudited consolidated financial results for the first half of the fiscal year ended March 31, 2024 (the "first half of fiscal year 2024") (Press release, Yisheng Biopharma, JAN 22, 2024, View Source [SID1234639417]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. David Shao, Director, President, and CEO of the Company, commented, "During the first half of fiscal year 2024, though we continued to experience the lingering impact of inventory issues from previous COVID-related disruptions at our YSJA rabies vaccine manufacturing facilities, we executed various operational enhancements to overcome past setbacks. By improving our raw material supply, refining our inventory management, and optimizing the production throughput, our vaccine production operation has returned to normal, and our inventory situation is improving. With higher production throughput and a healthier inventory level of finished products, we expect that the second quarter of our fiscal year 2024 will be the last to be impacted by the previously incurred production delays. Meanwhile, we expect YSJA rabies vaccine revenues in the third quarter, ended December 31, 2023, to increase approximately 50% sequentially from the second quarter, ended September 30, 2023. Our promising array of product candidates are advancing in the development, and we are optimistic about the potential of our PIKA rabies vaccine to provide us with an important new advantage."

"At the same time, we are fortifying our corporate governance and streamlining our decision-making process to bolster our foundation for long-term and sustainable growth," Dr. Shao continued. "We have taken steps to diversify our Board composition with the addition of global pharmaceutical industry leadership and US capital market expertise to our company, a move which has thus far been lauded by our shareholders. Under the stewardship of our board of directors, we will continue to innovate and capitalize on resurgent demand from the market."

Ms. Brenda Wu, CFO of the Company, added, "For the first half of fiscal year 2024, our revenues were RMB273.1 million, mainly due to COVID-related disruptions affecting raw material supply chains, manufacturing operations, and production output at our YSJA rabies vaccine production facilities. Our gross profit for the period was RMB220.9 million, and we expanded our gross profit margin by 4.3 percentage points to 80.9%. Our cash and cash equivalents totaled RMB259.9 million at the end of the period. Looking ahead, we will continue to strategically enhance our business and capitalize on growth opportunities as we strive to deliver long-term value for our shareholders."

Business Updates

YSJA Rabies Vaccine

YS Biopharma’s marketed vaccine product, YSJA rabies vaccine, was the first aluminum-free lyophilized rabies vaccine launched in China. Since the Company commenced production at its current GMP-compliant facilities in February 2020, and, since it commenced the product’s commercialization in late 2020, market intake of the Company’s YSJA rabies vaccine has been consistent and strong. As of September 30, 2023, YS Biopharma had sold more than 23.5 million doses of YSJA rabies vaccines to approximately 1,718 Chinese Center(s) for Disease Control and Prevention ("CDC") customers, which represents over 59.6% of CDC customers in China since October 2020.

Clinical Pipeline

YS Biopharma continues to advance its portfolio of innovative product candidates under various clinical development stages, including PIKA rabies vaccine, PIKA recombinant COVID-19 vaccine, PIKA YS-ON-001, and PIKA YS-HBV-002.

PIKA Rabies Vaccine

On October 31, 2023, the Company announced that it had completed the enrollment of subjects in its Phase III clinical trial of the PIKA rabies vaccine. The trial includes a total of 4,500 participants from Pakistan and the Philippines, and will assess the safety, immunogenicity, and lot-to-lot consistency of the PIKA rabies vaccine. Interim results are expected in the first half of 2024.
PIKA Recombinant COVID-19 Vaccine

In March 2023, the Company reported positive interim safety and immunogenicity data for the PIKA recombinant COVID-19 vaccine from Phase II of the Phase II/III clinical studies which were completed in the Philippines and the UAE. The safety and efficacy of the Company’s PIKA adjuvant technology was validated in the Phase II/III trial, which involved roughly 6,000 participants. The Company anticipates that the results from the Phase III clinical trials will be released during the first half of 2024.
The Company will continue to monitor the evolving global situation surrounding COVID-19, and will utilize appropriate commercialization strategies for the PIKA recombinant COVID-19 vaccine accordingly.
PIKA YS-ON-001

PIKA YS-ON-001 is designed as an immunological therapeutical agent against cancers. The Company has completed the Phase I clinical trial of PIKA YS-ON-001 in China.
PIKA YS-HBV-002

On September 15, 2023, the Company announced that the United States Patent and Trademark Office had issued it a patent covering its PIKA YS-HBV-002, an immunotherapeutic vaccine designed to treat patients suffering from chronic hepatitis B virus (HBV) infection.
The Company expects to complete an Investigational New Drug (IND) application and commence the clinical development of PIKA YS-HBV-002 as a novel immunotherapy for the treatment of chronic HBV infection in 2024.
First Half of Fiscal Year 2024 Financial Results

Total Revenues

Total revenues were RMB273.1 million (US$38.0 million) in the first half of fiscal year 2024, compared to RMB399.5 million in the same period of fiscal year 2023, representing a decrease of 31.6%. This was primarily due to COVID-related disruptions affecting the Company’s manufacturing operations and production, which reduced batch approvals and doses available for sale; offset by the increases in product price by approximately RMB3.0 per dose.

Gross Profit

Gross profit was RMB220.9 million (US$30.8 million), representing an 80.9% gross margin, compared to RMB305.8 million, or a 76.5% gross margin, in the same period of fiscal year 2023.

Selling and Marketing Expenses

Selling and marketing expenses in the first half of fiscal year 2024 were RMB157.7 million (US$22.0 million), compared to RMB150.2 million in the same period of fiscal year 2023. This increase was primarily attributable to an increase in promotional and marketing services fees as the Company continued to promote its YSJA rabies vaccine.

General and Administrative Expenses

General and administrative expenses in the first half of fiscal year 2024 were RMB67.6 million (US$9.4 million), compared to RMB49.6 million in the same period of fiscal 2023. This change was primarily attributable to increases in 1) professional service fees, due to the Company’s status as a publicly-listed entity, 2) management salaries, and 3) provision for trade receivables and inventories.

Research and Development Expenses

Research and development expenses were RMB178.9 million (US$24.9 million) in the first half of fiscal year 2024, compared to RMB123.9 million in the same period of fiscal 2023. The increase was primarily driven by an increase in testing and clinical trial fees associated with the Company’s COVID-19 vaccine, PIKA rabies vaccine, and hepatitis B vaccines.

Net Loss

Net loss for the first half of fiscal year 2024 was RMB174.5 million (US$24.3 million), compared with RMB11.1 million in the same period of 2023.

Balance Sheet

As of September 30, 2023, the Company had cash and cash equivalents of RMB259.9 million (US$36.2 million), compared with RMB370.4 million as of March 31, 2023.

On January 22, 2024 NK CellTech Co., Ltd. (NK CellTech), a leading biotech company focused on the development of NK cellular therapies, reported that the FDA has granted clearance for the clinical trial of NK010, the non-genetically modified natural killer cells (Press release, NK CellTech, JAN 22, 2024, View Source [SID1234639416]). NK010 is the first non-genetically modified NK cells expended from allogeneic peripheral blood cell (PBMC) approved for clinical trial by the FDA from China.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

NK010 exhibits multiple high anti-tumor advantages including wide spectrum and high expression of NK cell activation receptors and high purity, which makes it possible to treat variety types of tumors. NK010 also shows the potential to treat non-tumor diseases and can be the best basal cell for a subsequent series of synthetic NK cell drugs (SynNK) developed by the company. The ovarian cancer was the first indication chosen for exploration in this Phase I clinical trial. Pre-clinical studies have shown outstanding potential, with NK010 exhibiting strong tumor growth inhibition on ovarian cancers in animal models, liver cancer and other solid tumors as well as acute myeloid leukemia.

"We are thrilled and proud to receive FDA clearance for the clinical trial of NK010," said Professor Zhigang Tian, Founder of NK CellTech and member of the Chinse Academy of Engineering and the Academia Europaea. "NK010 has demonstrated promising anti-tumor activity and safety in preclinical studies. We have great confidence in its potential to treat solid tumors. Yet, there is still a lot left to explore, and our team has remained on our mission to revolutionize cancer treatment through innovative cellular therapies and fulfill the unmet clinical needs in the future."

On January 22, 2024 Bold Therapeutics, a clinical-stage biopharmaceutical company developing novel metallotherapeutics, reported positive Phase 2 safety and efficacy data in advanced metastatic colorectal cancer (mCRC) patients treated with BOLD-100 in combination with FOLFOX previously treated with FOLFOX/CAPOX at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium on January 18-20, 2024 (Press release, Bold Therapeutics, JAN 22, 2024, View Source [SID1234639415]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Bold Therapeutics’ BOLD-100 is a first-in-class metallotherapeutic with a unique multimodal mechanism-of-action that targets a critical replication and survival pathway common across all cancers. Interim results presented at AACR (Free AACR Whitepaper) (April 2023) and ASCO (Free ASCO Whitepaper) (June 2023) showed robustly positive efficacy and safety results in advanced colorectal, biliary tract and gastric cancer patients.

Bold Therapeutics’ ongoing BOLD-100-001 (NCT04421820) study is a multinational Phase 2 clinical trial evaluating BOLD-100 in combination with standard-of-care FOLFOX (folinic acid / leucovorin, fluorouracil, and oxaliplatin) in patients with advanced gastrointestinal cancers. The trial has currently enrolled 109 patients with advanced biliary tract, colorectal, gastric, and pancreatic cancers at sites in Canada, the United States, Ireland, and South Korea. The primary endpoint for the trial is progression-free survival (PFS), with overall survival (OS) and objective response rate (ORR) as secondary endpoints. Disease control rate (DCR) was also captured.

As of an August 31, 2023 data cutoff, data from 36 patients with advanced metastatic colorectal cancer was presented in clinical poster format (abstract #143) entitled "BOLD-100-001 (TRIO039): A Phase 2 Study of BOLD-100 in Combination with FOLFOX in Advanced mCRC Patients Previously Treated with FOLFOX/CAPOX: Efficacy and Safety Analysis."

Key findings:

Enrolled patients had a median of 4 [range 2-8] prior therapies including FOLFOX/CAPOX
67% of patients had progressive disease on prior FOLFOX/CAPOX
Median progression-free survival (PFS) was 3.9 months [CI 2.7, 5.7]
Median overall survival (OS) was 9.6 months [CI 6.0, 17]
In 29 evaluable patients for response, the objective response rate (ORR) was 7.0%, with 2 partial responses (PR) and 20 stable diseases (SD) resulting in a disease control rate (DCR) of 76%
These findings indicate a clinical benefit for patients treated with BOLD-100 in combination with FOLFOX and on all metrics compares favorably to existing treatment options for advanced metastatic colorectal cancer: Taiho’s Lonsurf (trifluridine / tipiracil), Bayer’s Stivarga (regorafenib), and Takeda’s Fruzaqla (fruquintinib). The table below compares this data against the data from the registration studies for these existing treatment options, all of which had less progressed (and thus healthier) patient populations.

BOLD-100 in combination with FOLFOX continued to be well-tolerated, with no new safety signals. For all treated patients, treatment-emergent adverse events (TEAEs) were observed in 33 (92%) of patients, with the most common TEAEs as follows: neutrophil count decreases (all grade 47%, grade ≥3 42%), nausea (42%, grade ≥3 0%), and fatigue (19%, grade ≥3 0%).

"Not only are we encouraged with BOLD-100’s efficacy, but we are excited about BOLD-100’s unexpectedly favorable safety profile, which has allowed patients to remain on treatment considerably longer than originally expected and thus maximizes the impact of the treatment combination," noted Jim Pankovich, EVP of Clinical Development. "More specifically, relatively few patients in our study experienced neurotoxicity, despite all patients having been previously treated with neurotoxicity-inducing oxaliplatin."

Phase 2 safety and efficacy results in biliary tract and gastric cancer are currently available under confidentiality and will be presented publicly at a major cancer conference later this year.

"Bold Therapeutics was founded in 2018 to improve patient outcomes in some of the most difficult-to-treat cancer indications and has rapidly advanced since then" added E. Russell McAllister, CEO. "We look forward to advancing BOLD-100 into late-stage studies in the near-future, initially targeting a 2027 FDA approval in advanced metastatic colorectal cancer.

On January 22, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported that the U.S. Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA) for obecabtagene autoleucel (obe-cel) for patients with relapsed/refractory (r/r) Adult B-Cell Acute Lymphoblastic Leukemia (ALL) (Press release, Autolus, JAN 22, 2024, View Source [SID1234639414]). Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of November 16, 2024, a standard review timeline consistent with recently approved CAR T therapies. The FDA is not currently planning to hold an advisory committee meeting to discuss this application.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The BLA submission is based on data from the Pivotal Phase 2 FELIX study of obe-cel in adult r/r B-ALL. The data were presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2023, with updated data presented at the Annual Meeting of the American Society for Hematology Meeting (ASH) (Free ASH Whitepaper) in December 2023.

"Acceptance of the BLA filing is an important milestone for Autolus and we look forward to continuing our collaboration with the FDA during the review cycle," commented Dr. Christian Itin, Chief Executive Officer of Autolus. "With the PDUFA date set for November, we remain focused on preparing for the potential launch of obe-cel."

Autolus plans to submit a Marketing Authorization Application for obe-cel in relapsed/refractory ALL to the European Medicines Agency (EMA) in the first half of 2024.

Obe-cel has been granted Orphan Drug Designation by the FDA, Orphan Medical Product Designation by the EMA, Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA and PRIority MEdicines (PRIME) designation by the EMA for adult r/r B-ALL.

On January 22, 2024 Agenus Inc. (Nasdaq: AGEN), a leader in developing immunological cancer treatments, reported results from the NEST-1 study, an investigator-sponsored trial (IST) evaluating the combination of botensilimab and balstilimab (BOT/BAL) in the neoadjuvant setting for colorectal cancer (CRC), both those with Microsatellite Stable (MSS) CRC and Microsatellite Instability High (MSI-H) CRC (Press release, Agenus, JAN 22, 2024, View Source [SID1234639413]). Dr. Pashtoon Kasi, M.D., Director of Colon Cancer Research at Weill-Cornell Medicine, presented these findings at the ASCO (Free ASCO Whitepaper)-GI conference.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"BOT/BAL’s potential impact on colorectal cancer is groundbreaking. The study’s findings, particularly the significant tumor regression after only a single dose of BOT and two doses of BAL, and the complete elimination of ctDNA in 100% of patients tested, offer a potentially transformative treatment approach for CRC patients diagnosed with early stage and locally advanced colon and rectal cancers. These results hold great promise for patients and providers as a framework for reduced reliance on chemotherapy and/or surgical resection," said Dr. Pashtoon Kasi, M.D., Director of Colon Cancer Research at Weill-Cornell Medicine and lead investigator of the NEST-1 study.

Study Highlights:

Treatment Protocol: Patients received a single dose of BOT and two doses of BAL between diagnosis and surgery, which was approximately a four-week period.
Impressive Pathologic Response: Tumor shrinkage of ≥50% was observed in 67.5% of patients in the Microsatellite Stable (MSS) CRC cohort and 100% in the Microsatellite Instability-High (MSI-High) CRC cohort.
Surgery Without Delays: Treatment with BOT/BAL did not cause any postponements in surgical procedures, with only two instances of Grade 3 Treatment-Related Adverse Events (TRAEs) observed.
BOT/BAL Eliminates Circulating Tumor DNA (ctDNA): patients in the NEST-1 study were tested for ctDNA, a biomarker closely associated with long-term Disease-Free Survival (DFS).
In a separate, independent observational study of 1,792 patients (NCT04264702; View Source), also led by Dr. Kasi and presented at the ASCO (Free ASCO Whitepaper)-GI meeting on January 20th, showed a correlation between ctDNA clearance and improved disease-free survival (DFS) rates. Patients who remained ctDNA negative post-treatment exhibited better 2-year DFS as compared to ctDNA-positive patients.
Dr. Steven O’Day, Chief Medical Officer of Agenus, stated, "The NEST-1 trial results are remarkable. Neoadjuvant BOT/BAL in both MSS and MSI-H CRC resulted in marked tumor regression and robust immune cell infiltration in a very short interval. These results in MSS CRC (90% of all CRC) are particularly compelling and may lead to an unprecedented shift away from invasive and morbid standard treatments in the future."

NEST-1 data presented at the conference is available to view in the publications section of the Agenus website (View Source).

About Botensilimab

Botensilimab is an investigational multifunctional anti-CTLA-4 immune activator (antibody) designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 750 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.