On December 7, 2023 Bio-Thera Solutions, Ltd (688177:SH), a commercial-stage biopharmaceutical company developing a pipeline of biosimilars and innovative assets, reported that the United States Food and Drug Administration (FDA) has approved Avzivi (bevacizumab-tnjn), a biosimilar referencing Avastin (Press release, BioThera Solutions, DEC 7, 2023, View Source [SID1234638265]). Avzivi is Bio-Thera’s second USFDA approved product and is the second biosimilar researched, developed, and manufactured by a Chinese pharmaceutical company to receive FDA approval in the United States.

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The FDA approval of Avzivi was based on a comprehensive analytical, non-clinical and clinical data package submitted by Bio-Thera to the FDA. Extensive analytical characterization between BAT1706 and US and EU Avastin was conducted on structural, physicochemical, and biological properties to support biosimilarity of BAT1706. A randomized double-blind, single-dose, three-arm, parallel phase I study compared the pharmacokinetics, safety, and immunogenicity of BAT1706 with both the US and EU Avastin in healthy volunteers. A randomized, double-blind, three-arm parallel phase III study compared BAT1706 with Avastin for efficacy, safety, and immunogenicity in subjects with advanced non-squamous non-small cell lung cancer. The totality of the evidence demonstrated that BAT1706 has similar efficacy, safety, immunogenicity and quality as the reference product bevacizumab.

"Bevacizumab has been widely used in the treatment for lung and colorectal cancers and many other cancers around the world," commented professor Li Zhang, leading investigator for global phase III study of Avzivi. "The global phase III clinical trial has confirmed that Avzivi is highly similar to Avastin in terms of efficacy, safety and immunogenicity. The approval of Avzivi by the FDA will provide lung and colorectal cancer patients a new cost-effective treatment option. We hope Bio-Thera continues to make more high-quality biosimilars available to patients around the world."

"The approval of Avzivi is another landmark accomplishment for Bio-Thera as it marks Bio-Thera’s second FDA approved product in the United States," said Shengfeng Li, CEO at Bio-Thera. "As our biosimilar pipeline continues to mature, we intend to seek more approvals of biosimilars, expanding patient access to important therapies."

Bio-Thera and Sandoz entered into a license and commercialization agreement for Avzivi (BAT1706) in September 2021. Under the terms of the agreement, Bio-Thera is responsible for the development and manufacturing of the product. Sandoz is responsible for the commercialization of Avzivi in the United States and other countries around the world.

About Avzivi (bevacizumab-tnjn)
Avzivi (bevacizumab-tnjn) is a humanized monoclonal antibody that targets VEGF. It specifically binds to VEGF and blocks the binding of VEGF to its receptor, thereby reducing neovascularization, inducing the degradation of existing blood vessels, and thereby inhibiting tumor growth. The original company name for Avzivi is BAT1706. In the United States, Avzivi is indicated for the treatment of 1) Metastatic colorectal cancer in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment, 2) Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab product-containing regimen. (Limitation of Use: not indicated for adjuvant treatment of colon cancer), 3) Unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first-line treatment, 4) Recurrent glioblastoma in adults, 5) Metastatic renal cell carcinoma in combination with interferon alfa, 6) Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin, or paclitaxel and topotecan, 7) Epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent disease who received no more than 2 prior chemotherapy regimens.

ON December 7, 2023 Regor Therapeutics Group ("Regor"), a global innovator powered by cutting-edge drug discovery engine and differentiated clinical development pipeline, reported the results from Phase 1A single agent dose escalation study of RGT-419B, a next generation CDK4 inhibitor, in HR+ HER2- ABC patients who have progressed on prior CDK4/6is and ET (Press release, Regor Therapeutics, DEC 7, 2023, View Source;advanced-breast-cancer-patients-who-have-progressed-on-cdk46-inhibitors-and-endocrine-therapy-302009555.html [SID1234638264]). These results (cutoff date September 26, 2023) were presented today in poster session by Dr. Seth Wander from Massachusetts General Hospital at the San Antonio Breast Cancer Symposium (SABCS) taking place December 5-9, 2023, in San Antonio, Texas. The poster titled "First-in-human Phase 1A study of RGT-419B, a next generation CDK4 inhibitor, in patients with HR+/HER2- ABC who have progressed on prior CDK4/6 inhibitors (PO3-18-06; NCT05304962)", highlighted that:

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Across 12 patients with HR+HER2- ABC who have progressed on CDK4/6is and ET, RGT-419B administered as oral (PO) monotherapy in continuous 28-day cycles was safe and well-tolerated with no dose-limiting toxicities. No patients discontinued treatment with RGT-419B due to an adverse event.
The exposure of RGT-419B was dose proportional with long half-life and small peak to trough ratio at steady state.
RGT-419B demonstrated single agent efficacy in the heavily pretreated HR+/HER2- ABC patients who have progressed on CDK4/6i and ET. Three patients achieved partial responses and are still on treatment. 6 patients received treatment > 24 weeks.
The promising single agent efficacy of RGT-419B is consistent with the preclinical data from CDK4/6i resistant breast cancer models.
"RGT-419B demonstrates its potential to be the best-in-class next generation CDK4 inhibitor for HR+/HER2- breast cancer. The results presented today is encouraging because RGT-419B is not only safe and well tolerated, but also demonstrated single agent efficacy in heavily pre-treated HR+ HER2- ABC patients who progressed on the approved CDK4/6i and ET." said Xiayang Qiu Ph.D., Chief Executive Officer of Regor Therapeutics Group. "These data show that RGT-419B has monotherapy opportunity in HR+ HER2- ABC patients resistant to the approved CDK4/6i and ET. With the favorable safety profile and promising monotherapy efficacy, RGT-419B has best-in-class potential as a single agent or in combination in HR+HER2- BC patients resistant to CDK4/6i, and in earlier lines of treatments. Clinical studies of single agent dose expansion and combination of RGT-419B with ET are underway."

The Phase 1 trial (NCT05304962) is a multicenter, open-label study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of RGT-419B given as monotherapy or in combination with ET in patients with HR+HER2- ABC who have progressed on CDK4/6i and ET.

Copies of the posters are available on Regor’s website under the Science section.

On December 7, 2023 Bugworks Research Inc., a clinical-stage biopharmaceutical company, reported that it is presenting the research findings on its novel, best-in-class, dual-acting adenosine antagonists BWC2094 and BWC2562 with the potential to treat a variety of hard-to-treat cancers, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress 2023 in Geneva, Switzerland on 7th December (Press release, Bugworks Research, DEC 7, 2023, View Source [SID1234638263]).

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The poster highlights two lead molecules discovered from structure and property-guided drug discovery platform. The molecules demonstrate potent A2A/A2B dual antagonism across a variety of pathologically relevant models that recapitulate the high adenosine driven immunosuppression found in the tumour microenvironment (TME) across several cancers. To build differentiation and improve clinical translation, AI/ML driven virtual trials were employed to identify potential combination drugs, and to guide in patient selection during clinical development. BWC2094 and BWC2562 demonstrate synergistic activity in combination with approved cancer drugs in human peripheral blood assays and proprietary patient-derived ex vivo tumor explant platform as measured by a reduction in the tumor density and increased apoptosis/necrosis. Additionally, these molecules demonstrate good oral bioavailability in rodents and dogs and were found to be well tolerated for 14 days in dose-range finding toxicological studies in preclinical species. Based on the totality of evidence, BWC2094 is ready for IND submission.

Bugworks Research is at the forefront of developing novel small molecule drugs to combat hard-to-treat cancers and drug-resistant bacterial infections. The company is building a deep pipeline of differentiated oncology programs that target critical pathways involved in cancer progression and treatment evasion.

The ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress is an annual event offering a forum to present the latest scientific and clinical developments in immunotherapy to diverse stakeholders with an interest to deliver innovative treatments for cancer. Attendees are invited to visit the Bugworks poster on December 7th, 2023, between 12.00-1.00 CET.

On December 7, 2023 Applied DNA Sciences, Inc. (NASDAQ:APDN) ("Applied DNA" or the "Company"), a leader in PCR-based DNA technologies, reported consolidated financial results for its fourth quarter ended September 30, 2023 (Press release, Applied DNA Sciences, DEC 7, 2023, View Source [SID1234638262]).

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"Our fiscal fourth quarter concludes a productive year during which we took a number of critical steps that place us firmly in the execution phase of our pivot to a biotherapeutic manufacturing-first growth strategy," stated Dr. James A. Hayward, president and CEO of Applied DNA. "We closed on the strategic acquisition of Spindle Biotech that empowered the launch of our Linea IVT platform, initiated the build-out of an initial GMP manufacturing footprint to produce critical mRNA starting materials, acquired what we believe to be an enviable base of early-phase customers for both our Linea DNA and Linea IVT platforms, and affirmed our capacity for the rapid production of multi-gram quantities of Linea DNA. Cumulatively, these steps expand our relevance into the growing and diverse value chain of genetic medicine manufacturing with a near-term focus on enabling our customers to produce better mRNA faster.

"At our ADCL clinical lab and supply chain traceability segments, progress has been slower than hoped for due to the ongoing review of our pharmacogenomics assay and testing service by New York State Department of Health’s and as we pursue initiatives to migrate our seasonal cotton tagging business into a year-around revenue stream, respectively."

Continued Dr. Hayward, "Looking ahead to fiscal 2024, we believe that continued biotherapeutics segment momentum and anticipated continued expansion in genetic medicine manufacturing demand, particularly for mRNA, can drive segment growth in the coming fiscal year. Our optimism is founded in our proprietary Linea IVT platform that enables the cell-free, enzymatic production of critical mRNA starting materials with unprecedented flexibility, speed, scale, and costs. We believe that this platform offers the industry the ability to outperform conventional mRNA production processes at the exact time the industry is seeking differentiation and is embracing next-generation, fully enzymatic workflows."

"Furthermore, our planned GMP capacity for critical mRNA starting materials is expected to now come online in the first half of calendar 2024, subject to the availability of financing, that will for the first time enable us to support current and new customers’ migration to the clinic with mRNA drug candidates. We believe this capacity will be a catalyst for our procurement of larger-scale supply agreements for our platforms. Additionally, we will continue to invest for the future with a focus on platform optimization and data generation to enhance Linea DNA’s standing as an alternative source of DNA for all genetic medicines. While we expect fiscal 2024 to be a milestones-driven year for us given the biotherapeutics industry’s ongoing investment in mRNA, longer term, we believe the future of our Linea DNA platform is not constrained to critical starting materials for mRNA production and have already secured research use only orders and are starting to build a backlog for in vitro diagnostics, gene editing/therapy and adoptive cell therapy applications."

Summary Fourth Quarter Fiscal 2023 Financial Results:

Total revenues were approximately $780 thousand for the three-month period September 30, 2023, compared to $3.6 million for the same period in the prior fiscal year. The decrease in revenue of approximately $2.8 million was due to an expected decline in COVID-19 testing services revenue of $2.4 million driven primarily by cancellation of the testing contract with City University of New York (CUNY) in June 2023. The decrease was also due to a reduction in product revenue of $341 thousand. The decline in product revenues is primarily related to a decrease in the textiles market due to a decline year-over-year in cotton DNA tagging revenue.
Gross profit for the three-month period ended September 30, 2023, was $79 thousand, compared to $417 thousand for the three-month period ended September 30, 2022. The gross profit percentage was 10% and 12% for the three-month periods ended September 30, 2023, and 2022, respectively. The decline in gross profit year-over-year is due to a higher percentage of COVID-19 surveillance testing services revenue in the three-months ended September 30, 2022, that generated a higher gross profit compared to the same period in the current fiscal year.
Operating loss decreased to $4.2 million for the three-month period ended September 30, 2023, as compared to $4.3 million for the fourth quarter of fiscal 2022. The decrease in operating loss is the result of lower operating expenses during the fourth quarter of fiscal 2023 by $419 thousand, offset by the decline in revenue discussed above. The decrease in operating expenses was primarily due to a decrease in payroll and insurance expenses.
Net loss was $3.6 million for the three-month period ended September 30, 2023, compared to $665 thousand for the fourth quarter of 2022.
Excluding non-cash expenses, Adjusted EBITDA was a negative $3.5 million for the three-month period ended September 30, 2023, compared to a negative $3.4 million for the same period in fiscal 2022.
Cash and cash equivalents stood at $7.2 million on September 30, 2023, compared with $10.8 million as of June 30, 2023.
Fourth Quarter Fiscal 2023 Conference Call Information
The Company will hold a conference call and webcast to discuss its fourth quarter of fiscal year 2023 financial results on Thursday, December 7, 2023, at 4:30 PM ET. To participate in the conference call, please follow the instructions below. While every attempt will be made to answer investors’ questions on the Q&A portion of the call, not all questions may be answered.

To Participate, please ask to be joined to the ‘Applied DNA Sciences’ call:

Domestic callers (toll free): 844-887-9402
International callers: 412-317-6798
Canadian callers (toll free): 866-605-3852
Live and replay of webcast: View Source

On December 7, 2023 Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, reported the initiation of enrollment for its Phase 1 clinical trial of XTX101, an investigational tumor-activated, Fc-enhanced anti-CTLA-4, in combination with atezolizumab and reported updated monotherapy data from its ongoing Phase 1 clinical trial evaluating XTX101 in late-line patients with advanced and immuno-oncology (IO) refractory solid tumors (Press release, Xilio Therapeutics, DEC 7, 2023, View Source [SID1234638260]). The data were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress on December 7, 2023.

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"With the recent initiation of Phase 1 dose escalation for XTX101 in combination with atezolizumab, we look forward to establishing a recommended Phase 2 dose in support of our plans to evaluate the combination in a Phase 2 trial in patients with microsatellite stable colorectal cancer (MSS CRC), including patients with liver metastases where there is an especially significant unmet need," said Katarina Luptakova, M.D., chief medical officer of Xilio. "The new Phase 1 data we reported for XTX101, which include 18 patients treated at the recommended Phase 2 dose of 150 mg Q6W, continue to demonstrate XTX101’s promising safety profile with primarily Grade 1 or 2 treatment-related adverse events. In addition to the previously reported confirmed partial response in a non-small cell lung cancer patient through 36 weeks, these new data also suggest further evidence of monotherapy anti-tumor activity in late-line and IO refractory patients at the recommended Phase 2 dose."

Updated Data from the Ongoing Phase 1 Clinical Trial for XTX101

As of the data cutoff date of November 13, 2023, 36 patients with advanced solid tumors had been administered XTX101 monotherapy, including 18 patients at the recommended Phase 2 dose and schedule (RP2D) of 150 mg once every six weeks (Q6W).

Patients treated at the RP2D of 150 mg Q6W were heavily pre-treated, with 83% of patients receiving three or more lines of anti-cancer therapy and 56% previously treated with an immunotherapy.

Preliminary Safety Data

At the RP2D of 150 mg Q6W, 18 patients (including 9 patients previously reported) were evaluable for safety as of the data cutoff date:

● Safety data were consistent with previously reported results. XTX101 monotherapy was generally well-tolerated with treatment-related adverse events (TRAE) primarily Grade 1 or 2, and no patients discontinued treatment due to a TRAE. In addition, as previously reported, only one patient had a dose reduction due to an adverse event.
● The most common TRAE of any grade (≥10% incidence) reported by investigators was fatigue (11%).
● As previously reported, investigators reported only two Grade 3 TRAEs: Grade 3 TRAE of diarrhea, which occurred after two doses and resolved after five days without steroid use, and one Grade 3 TRAE of dermatitis.

In addition, as previously reported, no Grade 4 or 5 TRAEs were reported by investigators across all dosing levels and dosing intervals.

Preliminary Anti-Tumor Activity Data

At the RP2D of 150 mg Q6W, 12 patients were evaluable for anti-tumor activity as of the data cutoff date:

● As previously reported, a confirmed partial response (PR) was observed in a patient with Stage 4 PD-L1 negative non-small cell lung cancer (NSCLC), including complete resolution of liver metastases. The confirmed PR continued through 36 weeks of treatment with XTX101, with the patient discontinuing treatment after week 36 due to an unrelated adverse event.
● Additional data reported today demonstrated a disease control rate (DCR) of 33% in late-line and IO refractory patients administered XTX101 monotherapy at the RP2D of 150 mg Q6W, consisting of the confirmed PR in the NSCLC patient and stable disease in three patients (triple-negative breast cancer, melanoma and microsatellite stable colorectal cancer (n=1 each)).

Preliminary Pharmacokinetic Data

As previously reported, consistent with the tumor-selective design for XTX101, preliminary pharmacokinetic analyses demonstrated 96% activation of XTX101 in a melanoma tumor and 73% activation in a metastatic liver lesion in a colorectal cancer patient, compared to minimal peripheral activation of XTX101 of 13% in both patients.

Poster Presentation

A copy of Xilio’s data presentation from the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress for XTX101 is available in the "Our Approach—Publications and Presentations" section of the company’s website at www.xiliotx.com.

Clinical Development Plans for XTX101

Xilio recently completed enrolling patients at the RP2D of 150 mg Q6W in monotherapy dose expansion and initiated enrollment in Phase 1 combination dose escalation to evaluate the safety, tolerability and efficacy of XTX101 in combination with atezolizumab.

As previously reported, subject to obtaining sufficient additional capital, Xilio plans to:

● Complete Phase 1 combination dose escalation and select a RP2D for XTX101 in combination with atezolizumab in the second quarter of 2024
● Subject to the results of Phase 1 combination dose escalation, initiate a Phase 2 trial to evaluate the safety and efficacy of XTX101 in combination with atezolizumab in patients with MSS CRC in the third quarter of 2024

About XTX101 (anti-CTLA-4) and the Phase 1 Monotherapy and Phase 1/2 Combination Clinical Trials

XTX101 is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX101 for the treatment of adult patients with advanced solid tumors. Xilio has completed enrollment in monotherapy dose escalation (Part 1A) and monotherapy dose expansion (Part 1B). Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.

Xilio is currently evaluating the safety and tolerability of XTX101 in combination with atezolizumab (Tecentriq) in Phase 1 dose escalation in patients with advanced solid tumors, and subject to obtaining additional capital and the results of Phase 1 combination dose escalation, Xilio plans to evaluate the safety and efficacy of the combination in a Phase 2 trial in patients with microsatellite stable colorectal cancer (MSS CRC).