On August 15, 2023 Shuttle Pharmaceuticals Holdings, Inc. (Nasdaq: SHPH), a discovery and development stage specialty pharmaceutical company focused on improving outcomes for cancer patients treated with radiation therapy (RT), reported a corporate update in connection with the filing of its Quarterly Report on Form 10-Q for the quarter ended June 30, 2023 (Press release, Shuttle Pharmaceuticals, AUG 15, 2023, View Source [SID1234634438]).

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Recent Highlights

On track to commence Phase II clinical study in the fourth quarter of 2023 for Ropidoxuridine, Shuttle Pharma’s lead clinical sensitizer drug candidate.
Successfully completed the initial manufacturing campaign for the active pharmaceutical ingredient (API) of Ropidoxuridine for use in the Shuttle Pharma’s upcoming Phase II clinical trial.
Received approval for a Type B pre-IND meeting with the FDA for guidance on the proposed Phase II clinical trial with a goal of receiving written responses from the FDA by September 18, 2023.
Moved into new laboratory and office space to assist in furthering the development Shuttle Pharma’s lead drug candidates and accelerate broader diagnostic capabilities on predictive biomarkers.
Q2 2023 operating expenses (excluding non-cash items) totaled $1.5 million.
At June 30, 2023, Shuttle Pharma’s cash balance was $8.4 million (including cash, cash equivalents and marketable securities).

"We are making significant progress in the advancement of Ropidoxuridine, our lead clinical sensitizer drug candidate, for treatment in brain cancer patients undergoing radiation therapy. During the last few months, we successfully completed the initial manufacturing campaign for the API to be used in the upcoming Phase II clinical trial and received approval from the FDA for a Type B pre-IND meeting to receive guidance on the trial design," commented Shuttle Pharma’s Chairman and CEO, Anatoly Dritschilo, M.D. "We expect to receive comments from the FDA by mid-September which would put us in position to initiate the clinical trial in the fourth quarter of this year — a significant inflection point in the development of Ropidoxuridine."

"The move into our new laboratory will accommodate not only our Ropidoxuridine research efforts, but also enhance our ability to establish a CLIA laboratory to advance our diagnostic intellectual property that has been developed with funding from NIH small business innovative (SBIR) research contracts over the past several years, particularly for our predictive biomarker capabilities for prostate cancer patients. We are eligible for NIH SBIR ‘bridge’ support to assist in funding the advancements of these efforts. Our recently published work in premier cancer journals provides insight into the immune response taking place in patients after radiation therapy for cancer and informs therapeutic strategies for sequencing radiation and immune therapy modalities for cancer treatment," Dr. Dritschilo concluded.

On August 15, 2023 YS Biopharma Co., Ltd. (NASDAQ: YS) ("YS Biopharma" 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 financial results for the first quarter of the fiscal year ended March 31, 2024 (the "first quarter of fiscal year 2024") (Press release, Yisheng Biopharma, AUG 15, 2023, View Source [SID1234634437]).

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Dr. David Shao, Director, President, and CEO of YS Biopharma, commented, "During the first quarter of fiscal year 2024, our top-line came under pressure from tight inventory levels of finished products available for sale, caused by the lingering impacts of COVID-related disruptions at our YSJA rabies vaccine manufacturing facilities. While these disruptions occurred in late 2022 and early 2023, the long and complex nature of the vaccine manufacturing process means that we are experiencing the impact at present. In the first quarter, we took several steps to enhance our operations and ensure future stability, including boosting manufacturing productivity, building out our sales network, and streamlining research and development efforts. Demand for our YSJA rabies vaccine remains robust, and we continue to bring our pipeline of promising product candidates, including our next generation PIKA rabies vaccine, towards commercialization. We are confident that we will overcome the near-term difficulties we have faced, and we believe we are well-positioned for sustainable, long-term success."

Ms. Brenda Wu, CFO of YS Biopharma, added, "In the first quarter of fiscal year 2024, our total revenues were RMB176.3 million, as we continued to deal with the fallout of COVID-related disruptions on our supply chains and manufacturing operations. Our gross profit for the quarter was RMB141.6 million, and we recorded a solid gross profit margin of 80.3%. As of the end of the first quarter, our balance sheet remains strong, and we plan to diligently monitor our expenses in order to create a stable foundation for our long-term growth. We are confident in our business model and excited for the opportunities the future holds."

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 June 30, 2023, YS Biopharma had sold more than 22.2 million doses of YSJA rabies vaccines to approximately 1,725 CDC customers, which represents over 60% of CDC customers in China.

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, and PIKA YS-ON-001.

PIKA Rabies Vaccine

As of June 1, 2023, the Company had been granted approval by regulatory bodies in the Philippines, Singapore, and Pakistan to undertake Phase III clinical trials of the vaccine. This multi-country Phase III study is a registration trial and will evaluate the vaccine’s ability to induce an immune response and its safety profile.
The Company intends to include a total of 4,500 participants in the Phase III trial, with the recruitment process projected to commence in the fourth quarter of 2023. The Company aims to obtain interim results by early 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 the findings from the Phase III clinical trials will be released before the end of 2023.
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 enrollment of cancer patients for the Phase I clinical trial of PIKA YS-ON-001 in China. The Company expects the Phase I clinical trial will be completed by December 31, 2023.
First Quarter of Fiscal Year 2024 Financial Results

Total Revenues

Total revenues were RMB176.3 million (US$24.4 million) in the first quarter of fiscal year 2024, compared to RMB205.5 million in the same period of fiscal year 2023, representing a change of 14.2%. This was primarily due to COVID-related disruptions affecting raw material supply chains, manufacturing operations, and production output at the Company’s YSJA rabies vaccine production facilities, which negatively impacted batch approvals and doses available for sale.

Gross Profit

Gross profit was RMB141.6 million (US$19.6 million), representing an 80.3% gross margin, compared to RMB154.3 million, or a 75.1% gross margin, in the same period of fiscal year 2023.

Selling and Marketing Expenses

Selling and marketing expenses in the first quarter of fiscal year 2024 were RMB79.2 million (US$11.0 million), compared to RMB70.5 million in the same period of fiscal year 2023. The increase in selling and marketing expenses reflects the Company’s ongoing long-term strategies to enhance promotional and marketing services in order to expand and strengthen its distribution network of district- and county-level CDCs and hospitals. This targeted expansion aligns with the Company’s commitment to driving growth in key markets.

General and Administrative Expenses

General and administrative expenses in the first quarter of fiscal year 2024 were RMB31.8 million (US$4.4 million), compared to RMB25.5 million in the same period of 2023. This change was primarily attributable to higher professional service fees associated with the Company’s status as a publicly-listed entity.

Research and Development Expenses

Research and development expenses were RMB100.6 million (US$13.9 million) in the first quarter of fiscal year 2024, compared to RMB70.3 million in the same period of 2023. The change was primarily driven by an increase in preclinical and clinical development costs associated with the Company’s rabies vaccine pipeline. This increase reflects the Company’s targeted allocation of resources to advance its promising rabies vaccine candidates through various stages of development, in line with the Company’s commitment to innovation and addressing unmet medical needs.

Net Loss

Net loss for the first quarter of fiscal year 2024 was RMB69.5 million (US$9.6 million), compared with RMB19.6 million in the same period of 2023.

Balance Sheet

As of June 30, 2023, the Company had cash and cash equivalents of RMB311.8 million (US$43.1 million), compared with RMB370.4 million as of March 31, 2023.

Corporate Update

As part of its strategy to unlock the commercial potential of its vaccine franchise in underserved markets in Southeast Asia, the Company recently set up a new subsidiary in the Philippines to focus on clinical and regulatory efforts and product commercialization.

Conference Call Information

The Company’s management will hold an earnings conference call on Tuesday, August 15, 2023 at 8:00 P.M. Eastern Time to discuss the financial results. Listeners may access the call by dialing the following numbers:

United States Toll Free: 1-888-346-8982
International: 1-412-902-4272
Mainland China Toll Free: 4001-201203
Canada Toll Free: 1-855-669-9657
Hong Kong: 852-301-84992

The replay will be accessible through August 22, 2023 by dialing the following numbers:

United States Toll Free: 1-877-344-7529
International: 1-412-317-0088
Canada Toll Free: 855-669-9658
Access Code: 8167733

A live and archived webcast of the conference call will also be available at the Company’s investor relations website at View Source

On August 15, 2023 OnCusp Therapeutics, a biopharmaceutical company dedicated to transforming cutting-edge preclinical innovation into clinically validated treatments for cancer patients worldwide, reported the clearance of its Investigational New Drug (IND) Application for CUSP06 by the U.S. Food and Drug Administration (FDA) (Press release, OnCusp Therapeutics, AUG 15, 2023, View Source [SID1234634436]). CUSP06 is a highly differentiated, global second-in-class cadherin-6 (CDH6)-directed antibody-drug conjugate (ADC) designed for the treatment of multiple solid tumors.

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"We are delighted to announce the IND approval for our flagship program, CUSP06, which has demonstrated excellent anti-tumor efficacy across diverse in vivo cancer models with both high and low CDH6 expression," stated Dr. Bing Yuan, Chairman and CEO of OnCusp Therapeutics. "This achievement is a testament to the dedication and expertise of our exceptional team. As our first asset to receive FDA approval for clinical trials, this marks a transformative milestone for OnCusp and reaffirms our commitment to developing game-changing treatments for cancer patients."

CDH6 is overexpressed in a myriad of cancers such as ovarian, renal, uterine, thyroid, lung, and cholangiocarcinoma. CUSP06 is a highly differentiated CDH6 ADC that is thoughtfully engineered to enhance potency, amplify the "bystander effect," improve linker stability, and potentially overcome drug resistance. It has exhibited a robust safety profile and developability in IND enabling studies.

The Phase 1 clinical trial will assess the safety and tolerability of escalating doses of CUSP06 to determine the maximum tolerated dose and/or recommended dose for expansion in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors.

About CUSP06

CUSP06, a CDH6-targeting ADC, is composed of a proprietary antibody with high CDH6 binding affinity, a protease-cleavable linker, and an exatecan payload (a potent and clinically validated topoisomerase-1 inhibitor). The linker is specially designed to complement the exatecan payload, enabling a highly stable and homogenous ADC. The payload is a weak substrate for BCRP/P-gp, which are drug efflux pumps that drive chemoresistance to many therapies. In preclinical data, this linker/payload has been shown to have a stronger "bystander effect" than competitor ADCs. CUSP06 has a drug-to-antibody ratio of 8. OnCusp obtained the exclusive global rights (ex-China) to lead the development and commercialization of CUSP06 from Multitude Therapeutics. WuXi XDC, a global CRDMO company dedicated to end-to-end bioconjugates services, is the CMC partner for CUSP06.

On August 15, 2023 Thryv Therapeutics Inc., a clinical stage biotechnology company developing therapies for rare diseases including Congenital Long QT Syndrome (LQTS), atrial fibrillation, and resistant cancers, reported FDA clearance of its Investigational New Drug application (IND) for THRV-1257 (Press release, Thryve Therapeutics, AUG 15, 2023, View Source [SID1234634435]). THRV-1257 is being investigated for the treatment of advanced Anaplastic Thyroid Cancer (ATC), including those patients with the common BRAF mutation V600E. The first in human study will determine the optimal dosing of THRV-1257 in patients with solid tumors, followed by treatment in combination with approved cancer therapies.

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At the same time, the company announces acceptance of a late breaking poster that will be presented at the upcoming American Thyroid Association (ATA) annual meeting in Washington DC, on September 30th, 2023, from 10:00 a.m. to 1:00 p.m. The presentation will highlight in vitro and in vivo preclinical results of SGK1 inhibition in models of ATC.

"Preclinical evaluation of our SGK1 inhibitors uncovered novel biology and synergy with existing cancer treatments to extend their activity and reverse resistance. These studies have revealed a significant opportunity to intervene in several oncology treatment paradigms with an SGK1 inhibitor" said Eric Campeau, Vice President, Translational Research.

According to the ATA, approximately 64,000 people in the United States are diagnosed with thyroid cancer each year. ATC makes up approximately 2% of these cases. Although ATC is rare compared to other thyroid cancers, it is one of the fastest growing and most aggressive of all cancers. Rapid evaluation and diagnosis are critical for ATC patients, as the disease manifests as a rapidly growing neck mass that impairs speech, swallowing and breathing. Activation of Serine and Glucocorticoid Kinase 1 (SGK1) was determined to be a critical component of ATC cell proliferation, including in tumor cell lines with mutated BRAF. Inhibition of SGK1 was unique in its capacity to suppress ATC cell proliferation compared to other inhibitors tested. Thryv Therapeutics is collaborating with expert scientists and oncologists in ATC to evaluate its SGK1 inhibitors as a potential treatment option to improve the outcome of people with this devastating disease.

"We are excited to advance our portfolio of potent SGK1 inhibitors into the treatment of aggressive, treatment resistant cancers. SGK1 has been implicated in a number of treatment-resistance oncology pathways and our work has demonstrated the potential to delay resistance and restore activity of approved therapies and ultimately improve progression free and overall survival outcomes," said Debra Odink, President, and Chief Development Officer.

On August 15, 2023 Servier, a leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported that the U.S. Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) and granted Priority Review for TIBSOVO (ivosidenib tablets) in the treatment of patients with isocitrate dehydrogenase 1 (IDH1)-mutated relapsed or refractory (R/R) myelodysplastic syndromes (MDS) (Press release, Servier, AUG 15, 2023, View Source [SID1234634434]). If approved, TIBSOVO would be a first-in-class targeted therapy option for MDS patients within this molecularly defined subset.

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"Servier continues to drive our leadership in the scientific innovation behind targeted mutant IDH inhibition, transforming the treatment landscape for thousands of patients living with difficult and hard-to-treat cancers," said Susan Pandya, M.D., Vice President Clinical Development and Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier. "This filing acceptance and Priority Review for TIBSOVO in patients with relapsed or refractory myelodysplastic syndromes underscores our continued work to advance therapeutic progress across IDH mutated cancers, and if approved in this setting, will bring the first and only targeted therapy to patients living with a significant unmet need."

The sNDA is based on key results from a pivotal Phase 1, open-label study in IDH1-mutated R/R MDS patients, in which TIBSOVO demonstrated durable remissions, including complete response in nearly 40% of patients, and an acceptable safety profile. The updated efficacy results were presented at the 2023 European Hematology Association (EHA) (Free EHA Whitepaper) Congress.

These findings showed that in the efficacy analysis set (n=18), a complete remission (CR) rate of 38.9% and objective response rate (ORR) of 83.3% were documented in patients treated with TIBSOVO. In addition, the median time to CR was 1.87 months (range: 1.0, 5.6). At the time of data cutoff, the median duration of CR had not been reached (range: 1.9, 80.8*) and the median overall survival was 35.7 months (range: 3.7*, 88.7*). Additionally, of the nine patients who were transfusion dependent with red blood cells or platelets at baseline, 66.7% (n=6) became independent of transfusions during any ≥56-day post-baseline period. Overall, treatment-related adverse events were consistent with the known safety profile of TIBSOVO. There were no new safety signals identified in this study.

"While the novel use of targeted IDH inhibition has been proven across a number of difficult-to-treat cancers, there continues to be a significant unmet need for MDS patients within this molecularly defined subset, especially for those who experience disease progression," said Amir Fathi, M.D., Program Director, Center for Leukemia at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School. "Today’s filing acceptance provides further support for the potential efficacy and acceptable safety profile of TIBSOVO in relapsed or refractory MDS and reinforces the importance of mutational testing in this patient population."

Priority Review is granted to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis, or prevention of serious conditions.1

FDA Breakthrough Therapy designation was previously granted for TIBSOVO for the treatment of adult patients with R/R MDS with a susceptible IDH1 mutation as detected by an FDA-approved test.

* Denotes a censored observation.

About the NCT02074839 Clinical Trial2
This Phase I, open-label multinational study evaluated the safety, tolerability, and clinical activity of ivosidenib in patients with relapsed or refractory myelodysplastic syndromes with an IDH1 mutation. The primary endpoint was complete remission (CR) plus partial remission (PR) rate and key secondary endpoints included duration of CR plus PR, duration of transfusion independence, and time to transfusion independence.

About TIBSOVO (ivosidenib tablets)
TIBSOVO is currently approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory AML and in monotherapy or in combination with azacitidine for adults with newly diagnosed IDH1-mutant AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. TIBSOVO was recently approved by the European Commission as a targeted therapy in two indications: in combination with azacitidine for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) with an isocitrate dehydrogenase-1 (IDH1) R132 mutation who are not eligible to receive standard induction chemotherapy; as well as in monotherapy for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation who were previously treated by at least one prior line of systemic therapy. TIBSOVO has also been approved in the U.S. and Australia for patients with previously treated IDH1-mutated cholangiocarcinoma. TIBSOVO is also approved in China for the treatment of adult patients with relapsed or refractory AML who have a susceptible IDH1 mutation. Servier has granted CStone a co-exclusive license for the development and an exclusive license agreement for the commercialization of TIBSOVO in Mainland China, Taiwan, Hong Kong, Macao and Singapore.

About Myelodysplastic Syndromes
Myelodysplastic Syndromes (MDS) are disorders in which progenitor (stem) cells do not mature into healthy blood cells.3 In the U.S., approximately 16,000 new cases of MDS are reported each year,4 and one-third of those MDS patients will eventually progress to acute myeloid leukemia (AML).3 Approximately 3.6% of MDS patients have an IDH1 mutation, which have often been associated with worse overall outcomes and are considered early "driver" mutations in the progression of MDS to AML.5,6 Chemotherapy, supportive therapy, stem cell transplant, growth factors and similar medicines are used to treat MDS.