On March 28, 2023 TC BioPharm (Holdings) PLC ("TC BioPharm" or the "Company") (NASDAQ: TCBP) a clinical stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer, reported the pricing of a public offering of 3,437,500 of its American Depositary Shares (the "ADSs") (or pre-funded warrants in lieu thereof), together with Series C warrants (the "Series C Warrants") to purchase up to 3,437,500 of its ADSs at a public offering price of $1.60 per ADS (or pre-funded warrant in lieu thereof) and associated Series C Warrant (Press release, TC Biopharm, MAR 28, 2023, View Source [SID1234629465]). The Series C Warrants will have an exercise price of $1.75 per ADS, are exercisable upon issuance and will expire five years following the date of issuance. Each ADS representing one ordinary share of the Company. The closing of the offering is expected to occur on or about March 30, 2023, subject to the satisfaction of customary closing conditions. H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

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The gross proceeds to the Company from the offering are expected to be approximately $5.5 million, before deducting the placement agent’s fees and other offering expenses payable by the Company. The Company intends to use the net proceeds from this offering for working capital and general corporate purposes.

A registration statement on Form F-1 (File No. 333-270808) relating to these securities has been filed with the Securities and Exchange Commission, or the SEC, and was declared effective by the SEC on March 27, 2023. The offering will be made only by means of a prospectus, which is part of the effective registration statement. When available, electronic copies of the final prospectus may be obtained for free on the SEC’s website located at View Source and may also be obtained by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (212) 856-5711 or e-mail at [email protected].

The Company also has agreed that certain existing warrants to purchase up to an aggregate of 2,800,000 ADSs of the Company that were previously issued on November 30, 2022, at an exercise price of $5.00 per ADS and expiration dates of May 30, 2025 and May 30, 2028, will be amended effective upon the closing of the offering so that the amended warrants will have a reduced exercise price of $1.75 per ADS.

On March 28, 2023 Treatment of the first participant in a clinical trial of FLASH proton therapy for cancers in the bones of the chest has been completed at the Cincinnati Children’s/University of Cincinnati Medical Center Proton Therapy Center (Press release, Cincinnati Children’s Hospital Medical Center, MAR 28, 2023, View Source [SID1234629464]).

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FLASH is an investigational mode of radiation therapy delivery that can be administered to a patient in less than 1 second. Research in the laboratory suggests that FLASH may result in fewer side effects than standard forms of radiation delivery, and the clinical trial is testing the feasibility of FLASH to treat people with cancer.

The new study, called FAST-02, marks a significant achievement for the Proton Therapy Center in Cincinnati, which continues to lead the way in global research in the field of FLASH proton therapy.

FAST-02 follows a breakthrough last year in the world’s first clinical trial of FLASH proton therapy in people, the FAST-01 study (FeAsibility Study of FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases). That study focused on people with bone metastases in the extremities.

Now, Cincinnati Children’s researchers are collaborating with University of Cincinnati researchers to establish the efficacy of ultra-high dose rate proton therapy in treating painful bone metastases in the chest. The FAST-02 study is sponsored by Varian, a Siemens Healthineers company.

Ten adults whose metastatic cancer has spread to their chest bones will participate in the research clinical trial of FLASH proton therapy.

In pre-clinical testing, FLASH proton therapy has been shown to potentially reduce side effects of radiation treatment compared to conventional radiation. However, until recently, the technology to deliver FLASH radiation for cancer patients was not available.

"Our dedicated team of researchers, clinicians, and staff are committed to advancing the field of cancer treatment and finding new ways to improve patient outcomes," said John Breneman, MD, medical director of the Cincinnati Children’s/UC Medical Center Proton Therapy Center, who is principal site investigator for the FAST-02 clinical trial.

The Proton Therapy Center in Cincinnati is a state-of-the-art facility that features cutting-edge technology and equipment, allowing researchers to develop and test new treatments for a wide range of malignancies.

"This trial of an ultra-high dose rate of proton therapy is just one of our efforts to develop new and innovative cancer treatments," said John Perentesis, MD, who is research director of the Proton Therapy Center and director of oncology and cancer programs at Cincinnati Children’s. "Our goal is to establish a foundation for future potential trials in brain tumors, sarcomas, lymphomas, lung cancer, and other malignancies, and we are excited about the impact this research might have on cancer care."

Anthony Mascia, PhD, who is chief physicist at the Proton Therapy Center in Cincinnati, said: "The promise of FLASH is to be able to deliver treatment at ultra-high dose rates with potentially fewer side effects. We currently are doing research studies into its efficacy, which, if confirmed, could transform radiation oncology."

The $126 million Cincinnati Children’s/UC Medical Center Proton Therapy Center incorporates a $24 million, one-of-a-kind research facility, which includes integrated laboratories and a fully operational proton treatment room dedicated exclusively for research. In addition, children and adults from around the world receive treatment for more than 30 types of cancer in the two clinical proton therapy rooms.

The Proton Therapy Center on the Liberty Campus of Cincinnati Children’s is one of only a few facilities in the world that can deliver FLASH proton therapy in a clinical setting. With this latest clinical trial, the medical center continues to push the boundaries of cancer treatment – and to offer hope to patients and families affected by this devastating disease.

On March 28, 2023 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), reported its full-year 2022 financial results and provided updates on key events and achievements since the start of 2022 (Press release, Antengene, MAR 28, 2023, View Source [SID1234629463]).

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1. Sales Revenue Reached 5.6 Times Year-Over-Year while the Adjusted Loss Narrowed by 10.3%

– XPOVIO (selinexor), Antengene’s first commercialized product and the world’s first oral XPO1 inhibitor leveraging a novel mechanism of action, generated a total of RMB160 million in revenue in 2022, a sum amounted to 5.6 times of 2021 (the product was commercially launched in Mainland of China on May 13, 2022).

– As a result of the strong revenue growth, the adjusted loss for 2022 was narrowed by 10.3%.

2. First/Best-in-Class Potential Clinical Programs as Value Drivers for Future Growth of Antengene

– Antengene has built a pipeline of 9 oncology programs at various stages going from clinical to commercial, including 6 with global rights, and 3 with rights for the APAC region. Some of these assets, such as ATG-031 (anti-CD24 antibody), have first-in-class potentials; while others, such as ATG-008 (mTORC1/2 inhibitor), ATG-037 (CD73 inhibitor), ATG-101 (PD-L1/4-1BB bispecific antibody), ATG-008 (ATR inhibitor), ATG-022 (Claudin 18.2 antibody-drug conjugate), and ATG-017 (ERK1/2 inhibitor), have best-in-class potentials. These assets are currently being evaluated in a total of 16 clinical trials around the world.

– Clinical achievements in 2022 and early 2023 include obtaining 7 IND approvals and an Orphan Drug Designation, as well as the dosing of the first patient in 5 studies.

– Released results from 16 preclinical and clinical studies at 7 renowned international congresses and medical journals including the AACR (Free AACR Whitepaper), ASCO (Free ASCO Whitepaper), SITC (Free SITC Whitepaper), CSCO, EHA (Free EHA Whitepaper), ASH (Free ASH Whitepaper) and BMC Medicine.

3. Fast-Growing Pan-APAC Commercialization of XPOVIO

– The commercialization network for XPOVIO in China now covers 600 hospitals and over 120 direct-to-patient (DTP) pharmacies in over 30 provinces and autonomous regions, and municipalities. XPOVIO attained 34 urban-customized commercial health insurance listings (Huiminbao).

– 6 XPOVIO regimens received a total of 27 inclusions or upgraded recommendations by 7 major clinical guidelines and evidence-based studies. In addition, XPOVIO was also included into 2 Guiding Principles for Clinical Applications and expert consensuses.

– In 2022, XPOVIO obtained NDA approvals in 3 markets including Australia, Singapore, and Taiwan, China. In addition, Antengene secured the first APAC reimbursement listing for XPOVIO by the Pharmaceutical Benefits Scheme (PBS) in Australia. NDAs for XPOVIO were submitted in 3 other countries and regions including Macau, China, Thailand, and Malaysia.

– In 2023, Antengene expects XPOVIO to be approved in Hong Kong, China and Macau, China and plans to submit an NDA for XPOVIO in Indonesia. Moreover, the company also plans to submit a supplementary New Drug Application (sNDA) for XPOVIO for the treatment of patients with diffuse large B-cell lymphoma (DLBCL) in Mainland of China.

4. High Profile Clinical Trial Collaborations in 2022

– Entered into a clinical collaboration with BeiGene on a Phase I/II study evaluating XPOVIO in combination with tislelizumab in patients with T and NK-cell lymphoma.

– Entered into a clinical collaboration with MSD on the Phase I STAMINA-001 trial designed to evaluate ATG-037 in combination with pembrolizumab in patients with locally advanced or metastatic solid tumors.

5. A Strong Cash and Bank Balance to Provide Runway Beyond 2025

– As of December 31st, 2022, the company has a cash and bank balance of about RMB1.8 billion. This strong cash and bank balance, together with the strong near-term revenue growth potential of XPOVIO and careful spending, enables the continuous growth, development, and operation of Antengene beyond 2025.

"In 2022, we made notable strides on multiple fronts of our business. The revenue from our lead product, XPOVIO, reached RMB160 million in 2022, a sum amounted to 5.6 times year-over-year. Meanwhile, we delivered crucial milestones in drug discovery and development, with a number of our potential BIC/FIC programs already entered clinical studies in Australia, Mainland of China, and the U.S. We expect these clinical programs to begin yielding results sometime during 2023 and 2024," said Dr. Jay Mei, Antengene’s Founder, Chairman and CEO. "This impressive performance is a testament to the highly effective global collaboration by our commercial teams and the company’s strong capabilities in drug discovery and development. Moreover, we expect our cash and bank balances totalling about RMB1.8 billion to support Antengene’s planned operations and revenue growth beyond 2025. Moving forward, we will continuously strive to become a leading multinational biopharmaceutical company with a portfolio of commercialized products, committed to improving the quality of life for cancer patients and creating value for our shareholders and partners."

On March 28, 2023 Mount Sinai Medical Center (MSMC) reported the results of a clinical trial led by Brian Slomovitz, MD, Professor of Obstetrics/Gynecology and Division Director at Mount Sinai Medical Center in Miami Beach, Florida (Press release, Mount Sinai Hospital, MAR 28, 2023, View Source [SID1234629462]). The investigator-initiated phase II trial, sponsored by the GOG Foundation, investigated the combination of ribociclib and letrozole in patients with recurrent low-grade serous ovarian cancer (LGSOC) (GOG-3026) presenting positive results that will change the standard of care for this cancer moving forward. As the Principal Investigator for this trial, Dr. Slomovitz presented the results at The Society of Gynecologic Oncology’s 2023 Annual Meeting on Women’s Cancer in Tampa, Florida.

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Ribociclib and letrozole combination is active in patients with advanced or recurrent LGSOC: Phase II trial results:

ORR, PFS, DOR compare favorably to most active agents previously investigated.
In this trial, the reported response rate was 23%, the progression-free survival 19.1 months, and the duration of response of 19.1 months. Sixty-four percent of evaluable patients experienced a reduction in target tumor size.

"These results are promising. Women with this disease have limited treatment options. The progression-free survival and duration of response are both 6 months greater than what we have observed with the current standard treatments," stated Dr. Slomovitz. LGSOC is a rare subtype of ovarian cancer, which typically occurs in younger women and may arise from a non-invasive precursor disease (serous borderline tumor). Approximately 80% of women with LGSOC suffer disease recurrence following primary therapy. Traditional treatment options, including chemotherapy, hormonal therapy, and biologic targeted therapies, have limited clinical efficacy and short durations of response. In particular, response rates to chemotherapy range from 0-15%. Treatment options for women with recurrent disease remains an unmet need.

Dr. Slomovitz added, "Our next steps are to compare this regimen of ribociclib and letrozole vs the best current therapies in a head-to-head study. Hopefully this work can lead to an FDA approval for this combination."

Mount Sinai Medical Center is excited about this promising advancement for gynecologic cancer patients dealing with rare tumors. This is yet another opportunity to help transform the standard of care in gynecologic oncology.

On March 28, 2023 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune, ophthalmology and other major diseases, reported its 2022 annual results and major company business updates (Press release, Innovent Biologics, MAR 28, 2023, View Source [SID1234629461]).

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Dr. Michael Yu, Founder, Chairman and CEO of Innovent, stated: "2022 was the first year for Innovent’s second decade in business. Despite challenges amid COVID and macro environments in the year, we are taking initiative to make profound improvements and strengthen our foundation for more sustainable growth, as we believe efficiency improvement, sustainable growth and technology innovation will be more emphasized in the biopharmaceutical industry. During the year, we built a more diversified commercial portfolio and further improved our commercial operational efficiency. Our strategical position in several key non-oncology areas brings us another important pillar of our future business growth. We further strengthened innovation with extended Innovent Academy technology and multiple international collaborations. Looking ahead, Innovent will strive to achieve our strategic goals of sustainable growth and global innovation, through further expansion of commercial portfolio, improvement of operational efficiency, and innovation through advanced R&D platform for the global market. We will uphold the vision of ‘to become a global premier biopharmaceutical company’ and create sustainable value for patients, employees, shareholders and the society."

Commercial – Continuous portfolio expansion and efficiency improvement achieved

Expansion of commercial portfolio into eight approved products, including: TYVYT, BYVASDA, SULINNO, HALPRYZA, PEMAZYRE, Olverembatinib, CYRAMZA (new product) and Retsevmo (new product).
Product revenue RMB4,139 million in year 2022: an increase of 3.4% compared with the prior year with fast ramp-up of product volume and contribution of new products despite impact of COVID and price reduction of TYVYT (sintilimab injection) during 2022.
NRDL coverage further expanded, benefiting broader patient groups: In January 2023, two additional indications of TYVYT (sintilimab injection), olverembatinib for the first listing, and multiple additional indications of BYVASDA (bevacizumab injection), HALPRYZA (rituximab injection), and SULINNO (adalimumab injection) were included in the updated NRDL.
Broad coverage in commercial channels and networks with an experienced and professional sales and marketing team: expansive coverage of over 5,000 hospitals and a well-structured commercial team of nearly 3,000 talents. The Company is also strategically establishing commercial presence in certain non-oncology therapeutic areas for more diversified and long-term growth.
Improved efficiency in commercial operation with preliminary results observed:
The Company continuously develops a more sustainable and healthier commercial management model, which could further improve operational efficiency and expand the scale of business for long-term sustainable business growth.
In the past year, preliminary positive results were observed: the ratio of sales and marketing expenses to total product revenue (under IFRS measurement) decreased from 65.5% in 2021 to 62.6% in 2022, and from 68.5% in the first half of 2022 to 56.9% in the second half of 2022, in particular.
Pipeline – Expand the boundary of novel oncology therapies, and roll out non-oncology high-potential products

We have built a strong pipeline with over 30 innovative drug candidates, among which 8 products are approved, 3 assets are currently under NDA review by the NMPA, 5 assets are in Phase 3 or pivotal clinical trials, and approximately 20 assets in early Phase 1/2 clinical studies.

Oncology：Introduce novel modalities and therapies to expand the oncology pipeline

Submitted NDAs of two product candidates for the treatment of hematological malignancies, and have pioneered the development of three drug candidates for treatment of lung cancer:
IBI326 (BCMA CAR-T): the NDA was accepted for the treatment of r/r MM
IBI376 (PI3Kδ): the NDA was accepted for the treatment of r/r FL
IBI344 (ROS1/TRK): Ongoing pivotal Phase 2 for ROS1 positive NSCLC
IBI351 (KRASG12C): Ongoing pivotal Phase 2 for KRASG12C mutated NSCLC
IBI126 (CEACAM5 ADC): Ongoing Phase 3 for CEACAM5 highly expressed NSCLC
Received preliminary positive data for multiple global innovative molecules：
IBI110 (LAG3) : 1L sqNSCLC, 1L GC
IBI939(TIGIT): 1L NSCLC (PD-L1 TPS≥50%)
IBI188 (CD47): 1L MDS
Established a fully-integrated and differentiated ADC proprietary technology platform:
IBI343 (CLDN18.2 ADC) : Phase 1 multi-regional clinical trial ongoing in Australia and China. IBI343 has potential best-in-class profiles with differentiated design for potential wide therapeutic window and high potency.
More than 10 differentiated ADC projects in IND-enabling stage.
Non-Oncology：Strategically positioned in three major chronic diseases to accelerate the development of high-potential assets

Cardiovascular and metabolism ("CVM") field — high-potential innovative assets for multiple high-prevalence chronic diseases:
IBI306 (PCSK9): the NDA was accepted for the treatment of hypercholesteremia
IBI362 (GLP-1R/GCGR): Phase 2 study results in obesity and type 2 diabetes shows its best-in-class potential in weight loss, blood glucose lowering with favorable safety and multiple metabolic benefits. Phase 3 registrational studies for both indications have been initiated during late 2022 to early 2023.
IBI128 (XOI) : Phase 2 study (by LG Chem) data readout demonstrated its potential as best-in-class XOI for the treatment of hyperuricemia in gout patients, with overall superior efficacy and good safety profile. The Company plans to start a Phase 3 clinical study in 2023 in China.
IBI311 (IGF-1R) : Phase 2 study for the treatment of thyroid associated ophthalmopathy ("TAO") is ongoing and a Phase 3 registrational study will start in 2023.
Autoimmune field — capture differentiated clinical value and fulfill substantial unmet medical needs:
IBI112 (IL-23p19) : the Phase 2 data for IBI-112 (IL-23p19) demonstrated its potential long-lasting efficacy advantage and convenient extended dosing intervals for psoriasis. The Phase 3 registrational clinical study started in early 2023.
IBI353(PDE4): the multi-regional Phase 2b clinical study (led by UNION) of IBI353 in psoriasis reached positive topline results. Phase 2 clinical study in China will start in 2023.
Additional innovative autoimmune molecules such as IBI355 (CD40L) and IBI356 (OX40L) will enter first-in-human clinical studies in 2023 to explore other unmet medical needs in various types of autoimmune diseases.
Ophthalmology field — multiple differentiated bispecific antibodies:
IBI302(VEGF/C): Phase 2 studies of IBI302 for the treatment of nAMD are ongoing to explore potential effect in anti-macular atrophy.
IBI324 (VEGF-A/ANG-2) and IBI333 (VEGF-C/VEGF-A) are in the Phase 1 stage. The potential differentiation versus existing therapy brought by their innovative mechanisms and molecule designs as bispecific antibodies will be explored.
R&D: Global innovation continues as core long-term strategy

We continue to build Innovent Academy as an engine of innovation power:
In 2022, Innovent Academy has successfully delivered six high quality novel molecules into IND enabling stage.
Further enhance the R&D platform by leveraging the Company’s profound know-how in immunology, cancer biology and antibody engineering, with a focus on global innovation and cutting-edge technology extension.
Innovent Academy has built a fully integrated and differentiated ADC proprietary technology platform, which will gradually deliver next-generation ADC candidates into the clinical development stage to further enrich our long-term pipeline.
Deploy scientific and efficient approaches to early stage innovative pipeline development
Exploring the early-to-mid stage pipeline with global potential in ongoing PoC studies, with several molecules in the IO and ophthalmology fields.
Further explore the early clinical development of novel molecules with global potential, such as PD-1/IL-2, ADC clusters, etc, in multi-regional clinical trials.
BD: Strategic collaborations deepen overall strength of innovation

Entered into strategic collaboration with Sanofi to benefit more patients in China and Sanofi’s initial equity investment of EUR300 million in Innovent. Both companies are committed to accelerating the development and commercialization of clinical Phase 3 stage SAR408701 (tusamitamab ravtansine; anti-CEACAM5 ADC) and clinical Phase 2 stage SAR444245 (non-alpha IL-2) in China.
Expanded oncology strategic partnership with Lilly: Innovent obtained the sole commercialization right of Cyramza (ramucirumab) and Retsevmo (selpercatinib) in mainland China, and the right of first negotiation for potential future commercialization of pirtobrutinib (BTK inhibitor) in mainland China.
Launched antibody drug benefiting emerging markets: BYVASDA (Indonesian trademark: Bevagen) was approved by the Indonesian Food and Drug Administration (BPOM) and is the first Chinese antibody drug commercialized and expected to be locally manufactured in Southeast Asia markets.
CMC：High-quality and scalable manufacturing capabilities

60,000L GMP certified production capacity which is currently the largest stainless steel bioreactor production capacity in China with more capacity construction in plan.
Quality compliance to GMP and cost advantage further strengthen market competitiveness.
Financial Highlights for the Year 2022

Total revenue was RMB4,556.4 million, an increase of 6.7% compared to the prior year.
R&D expenses were RMB2,871.2 million, an increase of RMB548.7 million from the prior year.
The ratio of selling and marketing expenses to produce revenue was 62.6%, a decrease of 2.9% compared to the prior year.
Loss for the year was RMB2,179.3 million, mainly due to continuous investment in R&D to support our long-term strategic goal of global innovation.
Cash and short-term financial assets was RMB9,166.0million, or approximately USD1.3 billion, which enables us to focus on the long-term sustainable development.