On March 28, 2023 Sirnaomics Ltd. (the "Company"; together with its subsidiaries, "Sirnaomics" or the "Group"; stock code: 2257), a leading biopharmaceutical company engaged in the discovery and development of advanced RNAi therapeutics, reported its audited annual results for the year ended 31 December 2022 (the "Year") (Press release, Sirnaomics, MAR 28, 2023, View Source [SID1234629468]).

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The Group’s loss for the year narrowed significantly from US$215.9 million in 2021 to US$97.4 million in 2022. The decrease in loss was primarily attributable to the decrease in loss on changes in fair value of financial liabilities at fair value through profit or loss (FVTPL) and listing expenses, though partly offset by the increase in research and development expenses and administrative expenses, which is in line with the Group’s continuous research and development efforts to support its steadily advancing and expanding pipeline of drug candidates.

Breakthroughs in Clinical-Stage Research and Development of Core Product Candidates

The Group has consistently strived to push the boundaries of innovation and continuously improved its technology platform. Two drug product formulations formulated with our PNP delivery platform have been evaluated for local therapeutic treatment (STP705) and systemic therapeutic treatment (STP707), both of which are currently undergoing late-stage clinical trials.

STP705

The interim results of the part-one Phase IIb clinical trial have demonstrated the efficacy of STP705 treatment, with the majority (78%) of the 32 patients evaluated achieving histological clearance. Impressively, the lowest dosage achieved 89% histological clearance. In the first quarter of 2023, the Group has commenced communication with the U.S. Food and Drug Administration (FDA) regarding its Phase III clinical study proposal for the treatment of isSCC.

STP705 for the treatment of BCC has demonstrated an improved cosmetic result with no significant cutaneous skin reaction and achieved an excellent safety profile with a 100% complete response using a 180 ug dosage. The Group has now completed the 240 ug dosage cohort and expects to have the final data readout in the second quarter of 2023. The latest results demonstrated very favourable efficacy without any drug related AEs and SAEs, further validating the broad potential of this drug candidate for the treatment of non-melanoma skin cancers and beyond.

Sirnaomics’ Phase I proof of concept clinical trial of STP705 for medical aesthetics treatment in adults undergoing abdominoplasty represents its first activity to apply an RNAi therapeutic candidate for localized fat remodeling. The Group expects interim data to be available in the second quarter of 2023 and the study should be completed in the second half of 2023.

Regulatory clearance for the Group’s IND application to participate in the global Phase I trial of STP705 for the treatment of patients with advanced liver tumors was granted by the Taiwan Ministry of Health and Welfare (TMHW) in July 2022 and the first patient will be initiated into the study during second half of 2023.

STP707

In February 2022, the Phase I clinical trial of STP707 for treating various solid tumor types was launched in the U.S. The interim data for the first three dosing cohorts was announced by the Group in December 2022. To date STP707 has demonstrated an excellent safety profile with the first three dosing cohorts and has exhibited a positive efficacy signal with many participants exhibiting the best response of stable disease with a meaningful number of participants remaining on study past the 100-day mark. In addition, this study has also been approved in the second half of 2022 to expand to Taiwan as part of the global multicenter clinical trial. The Group plans to expand oncology clinical studies in the Asia-Pacific, a region with a high unmet demand for innovative therapies.

Exciting Progress in IND Enabling Studies and Anticipated Clinical Studies

STP122G, the Group’s leading GalNAc-based therapeutic candidate targeting Factor XI, showed long-lasting target silencing activity, up to 28-week after one dose and in toxicology studies in mics and non-human primates. A U.S. IND was submitted in March 2023, and the Group is on track to start filing the clinical study application in the second quarter of 2023, if greenlight is given by the FDA.

RIM730, developed by RNAimmune Inc., a non-wholly owned subsidiary of the Group, comprises mRNA coding for a modified full length spike protein from the variant, and is formulated with LNP delivery technology for intramuscular administration. The Group expects to submit a U.S. IND in the first quarter of 2023.

Successful Commissioning of Guangzhou Facility Enables Flexibility and Capacity for Clinical Trials and Production Needs

Sirnaomics’ Guangzhou Facility successfully completed the full commissioning tasks with media fill simulation and trial run of STP705 in a lyophilized solid dose. During the Year, the Guangzhou Facility has supported the production of lyophilized toxicity lots for STP707, STP908, STP355 and STP369. With the recent full GMP batch of STP707 for human injection produced in the first quarter of 2023, the Guangzhou Facility is expected to be in full GMP-compliant manufacturing of pipeline products. In early 2023, the Guangzhou Facility initiated filling line capacity expansion to include liquid dose fill in 2R vial to support the Group’s GalAheadTM platform. An anticipated annual capacity of around 50,000 vials of lyophilized solid dose and 150,000 to 200,000 vials of liquid dose for human injectables dose capacity is sufficient to support all clinical trials the Group has currently planned.

Dr. Patrick Lu, Founder, Chairman of the Board, Executive Director, President and Chief Executive Officer of Sirnaomics said, "Over the years, we have been dedicated to enriching our innovative RNA drug product pipeline and taking it to the next level, as part of our commitment to improving the wellbeing of patients worldwide. 2022 was a remarkable year for us. We made significant strides in advancing the research and development of our core products, which help us solidify a leadership position in RNA medicine for cancer treatment on the global stage, and was recognized by the capital market through our selection as a constituent stock of the Hang Seng Composite Index. Looking ahead, we will focus on expanding our competitive advantages by advancing the development of our lead product candidates STP705 and STP707 through clinical trials and capitalizing on our dual proprietary delivery platforms furthering more innovative first-in-class preclinical assets into the clinical stage, and selectively pursuing synergistic partnership opportunities to maximize the potential of our clinical product candidates. We will also strive to secure sustainable value growth for our shareholders."

On March 28, 2023 Aadi Bioscience, Inc. (NASDAQ: AADI), a biopharmaceutical company focused on developing and commercializing precision therapies for genetically defined cancers with alterations in mTOR pathway genes, reported a corporate update and announced financial results for the fourth quarter and full-year 2022 (Press release, Aadi Bioscience, MAR 28, 2023, View Source [SID1234629467]).

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"2022 was a year marked by successive milestones with the launch of FYARRO, the start of the PRECISION 1 trial, strengthening our balance sheet with a $72.5 million financing, taking our cash runway into 2025, and collaborating on a new combination of nab-sirolimus with Mirati’s adagrasib," said Scott Giacobello, CFO and interim President and CEO of Aadi Bioscience. "We look forward to another year of advancements as we enter 2023 including the progression in our first collaboration, which is expected to initiate in the second quarter. As planned, we will provide preliminary data on patients in the PRECISION 1 trial in the second quarter of 2023."

Fourth Quarter 2022 Updates and Recent Operational Highlights

FYARRO net product sales were $5.2 million in the fourth quarter, or 23% sequential growth quarter-over-quarter, and were $15.2 million for full-year 2022, representing 10 months of sales.

Continued advancement of the PRECISION 1 registrational-directed trial in patients with tumor agnostic TSC1 and TSC2 inactivating alterations is advancing with continued enrollment and the Company plans to provide preliminary data on a meaningful number of patients in the second quarter of 2023.

Announced the appointment of Mohammad Hirmand, M.D., to Board of Directors. Dr. Hirmand is the co-founder of Avenzo Therapeutics, Inc., and serves as executive vice president and chief medical officer of this privately held biotechnology company focused on oncology therapeutics. Previously, Dr. Hirmand served as executive vice president and chief medical officer of Turning Point Therapeutics, a publicly traded precision oncology company, where he was responsible for clinical development, clinical operations and regulatory affairs, from December 2019 until its acquisition by Bristol Myers Squibb in August 2022.

Closed on a $72.5M financing during the fourth quarter, extending the Company’s cash runway into 2025.

Signed a clinical collaboration agreement during the fourth quarter with Mirati Therapeutics on combination of adagrasib with nab-sirolimus. The Phase 1/2 trial is expected to begin in the second quarter of 2023.
Fourth Quarter and Full-year 2022 Financial Results

Cash, cash equivalents and short-term investments as of December 31, 2022 were $172.6 million as compared to $148.9 million as of December 31, 2021, which is expected to fund operations into 2025 based on current plans.

Total revenue for the quarter ended December 31, 2022 was $5.2 million, and $15.2 million for the full-year ended December 31, 2022, resulting from sales of FYARRO.

Net loss for the three months ended December 31, 2022 was $13.9 million as compared to $16.0 million for the three months ended December 31, 2021. Net loss for the full-year 2022 ended December 31, 2022 was $60.5 million, as compared to $110.1 million for the period in 2021 (The prior year included the non-cash impairment charge of $74.2 million related to the acquired contract intangible asset incurred in conjunction with the Aerpio merger).
Conference Call Information

The Aadi management team is hosting a conference call and webcast today at 8:30 am ET (5:30 am PT) to provide a corporate update and discuss results for the fourth quarter and full-year 2022.

Participants may access a live webcast of the call on the "Investors & News" page of the Aadi Biosciences website at aadibio.com. To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the Company’s website for at least 30 days.

About FYARRO
FYARRO is an mTOR inhibitor indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).

About the PRECISION 1 Trial
The PRECISION 1 trial is a multi-center, open-label, tumor-agnostic pivotal study, of nab-sirolimus designed as a basket trial that will evaluate approximately 120 adult and adolescent patients with solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes. The trial will have two independent arms of 60 patients each to separately evaluate patients with either TSC1 or TSC2 inactivating alterations. Aadi has received Fast Track designation to evaluate nab-sirolimus in this indication from the FDA. The first patient in the PRECISION 1 trial was dosed in March 2022.

On March 28, 2023 Ratio Therapeutics Inc. (Ratio), a pharmaceutical company that employs a suite of innovative technologies to develop best-in-class radiopharmaceuticals for the monitoring and treatment of cancers, reported the licensing of a Granzyme B-targeted agent for PET imaging applications from Merck, known as MSD outside the United States and Canada (Press release, Ratio Therapeutics, MAR 28, 2023, View Source [SID1234629466]).

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Under the terms of the agreement, Merck will provide Ratio with several candidates and supporting preclinical and CMC data of its Granzyme B-targeted agent for PET imaging applications. Ratio will also be responsible for clinical development and will build a GMP production network for the PET imaging agent across North America, Western Europe, Japan, Australia, and beyond.

"We are thrilled to contribute our knowledge in nuclear medicine to advance the development of a novel imaging diagnostic in immunology and work alongside Merck, a global biopharmaceutical leader that has demonstrated a strong commitment to innovation and excellence for more than a century," said Dr. Jack Hoppin, Ratio’s Chairman and Chief Executive Officer. "The development of a Granzyme B-targeted agent for PET imaging has the potential to monitor responses to therapeutic interventions in clinical research."

Granzyme B is an enzyme released by activated immune cells, such as natural killer and cytotoxic T cells, with the primary function of killing tumor cells and normal cells infected with viruses. As such, Granzyme B holds potential to serve as a PET imaging biomarker to monitor immune cell activation in a variety of inflammatory diseases, autoimmune diseases, cancer and infection. The ability to visualize and quantify localized immune response empowers physicians to measure the early efficacy of therapies and modify treatment accordingly.

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.