On March 4, 2021 Synthetic Biologics, Inc. (NYSE American: SYN), a diversified clinical-stage company leveraging the microbiome to develop therapeutics designed to prevent and treat gastrointestinal (GI) diseases in areas of high unmet need, reported financial results for the year ended December 31, 2020 (Press release, Synthetic Biologics, MAR 4, 2021, View Source [SID1234576124]).

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Recent developments:

Received Institutional Review Board ("IRB") approval from Washington University School of Medicine in St. Louis for the SYN-004 (ribaxamase) Phase 1b/2a clinical trial protocol in allogeneic hematopoietic cell transplant ("HCT") recipients
Commenced screening of patients for enrollment of the first of three sequential antibiotic cohorts in the SYN-004 Phase 1b/2a clinical trial in allogeneic HCT recipients
Current cash position of approximately $72.6 million
Received $8.0 million from the exercise of warrants
Current cash runway provides funding into 2023 and ability to fully fund Phase 1b/2a clinical trial of SYN-004 and Phase 1 safety studies of SYN-020 intestinal alkaline phosphatase ("IAP") program
Upcoming milestones:

Expect to begin dosing patients in the first antibiotic cohort of the SYN-004 Phase 1b/2a clinical trial during Q1 2021; A topline data readout of the first antibiotic cohort is expected during Q4 2021
Expect to commence first Phase 1 single-ascending-dose study ("SAD") of SYN-020 during Q2 2021; Topline data anticipated during Q3 2021
Expect to commence second Phase 1 multiple-ascending-dose ("MAD") study of SYN-020 during Q3 2021; Topline data anticipated during Q2 2022
"We are more encouraged than ever by the outlook for the business as we have made important progress during the fourth quarter advancing and demonstrating the significant value of our clinical development programs. With a number of upcoming catalysts later this year, we believe there is potential to continue to deliver significant value for our shareholders," stated Steven A. Shallcross, Chief Executive and Financial Officer. "IRB approval by Washington University of the SYN-004 Phase 1b/2a clinical program protocol marks a major milestone for the Company. Looking ahead, we believe SYN-004 has the potential to address an important and underserved patient population, and may significantly improve outcomes for allogeneic HCT recipients by preventing downstream complications often associated with disruption of the gut microbiome by intravenous ("IV") beta-lactam antibiotics. We are pleased to announce that Washington University has begun screening patients for enrollment of the first of three sequential antibiotic cohorts and look forward to reporting topline data for this group towards the end of this year, pandemic conditions permitting."

Mr. Shallcross continued, "During the fourth quarter of 2020, we also made significant progress and gained additional clarity on potential clinical development pathways for our SYN-020 IAP program. Looking ahead, we intend to commence safety studies starting with a planned Phase 1 single-ascending-dose study in healthy volunteers during the second quarter of 2021; a topline data readout is expected during the third quarter of 2021. A second Phase 1 multiple-ascending-dose study is also expected to begin enrollment during the third quarter of 2021. Both studies are designed to support the advancement of SYN-020 in multiple potential therapeutic indications, including celiac disease, nonalcoholic fatty liver disease ("NAFLD") and age-related metabolic and inflammatory diseases. We are very excited about the potential for this program to be a long-term value driver for our Company and look forward to sharing important updates and progress as we continue to advance it towards clinical trials."

Mr. Shallcross concluded, "While remaining keenly focused on the execution of our clinical development activities, we also significantly strengthened our balance sheet and raised net proceeds of approximately $63.8 million, in addition to $8.0 million in proceeds from the cash exercise of warrants, which has helped to streamline our capital structure. As a result of these activities, our current cash position is approximately $72.6 million. Our fortified financial footing will now allow the Company to continue its operations into 2023 as well as fully fund the Phase 1b/2a clinical trial of SYN-004 and our planned Phase 1 safety studies of SYN-020 IAP."

Clinical Development and Operational Update

Announced approval by the IRB at Washington University of the SYN-004 Phase 1b/2a clinical program protocol in allogeneic HCT recipients, allowing the clinical trial to commence as planned;
Announced Washington University has begun screening patients for enrollment of the first antibiotic cohort for the Company’s Phase 1b/2a clinical trial of SYN-004 in allogeneic HCT recipients for the prevention of acute graft-versus-host-disease (aGVHD)
The Phase 1b/2a clinical trial comprises a single center, randomized, double-blind, placebo-controlled clinical trial of oral SYN-004 in up to 36 evaluable adult allogeneic HCT recipients,
The goal of this clinical trial is to evaluate the safety, tolerability and potential absorption into the systemic circulation (if any) of oral SYN-004 administered to allogeneic HCT recipients who receive an IV beta-lactam antibiotic to treat fever,
Study participants will be enrolled into three sequential cohorts and administered a different study-assigned IV beta-lactam antibiotic. Eight participants in each cohort will receive SYN-004 and four will receive placebo,
Safety and pharmacokinetic data for each cohort will be reviewed by an independent Data and Safety Monitoring Committee ("DSMC"), which will make a recommendation on whether to proceed to the next IV beta-lactam antibiotic,
A topline data readout for the first antibiotic cohort is anticipated during the fourth quarter of 2021, pandemic conditions permitting;
A Phase 1 SAD clinical trial in healthy volunteers of the Company’s SYN-020 IAP is anticipated to commence during the second quarter of 2021
A topline data readout is anticipated during the third quarter of 2021, pandemic conditions permitting,
A second Phase 1 clinical trial evaluating multiple-ascending doses of SYN-020 in healthy volunteers is expected to commence during the third quarter of 2021; topline data is anticipated during the second quarter of 2022, pandemic conditions permitting,
Both studies are intended to support the development of SYN-020 in multiple potential clinical indications;
Strengthened balance sheet by raising net proceeds of $63.8 million from the sale of the common stock via the Company’s At-The-Market ("ATM") facility, and $8.0 million resulting from the cash exercise of a portion of Company’s 2018 warrants
As a result of these activities, the Company has extended its cash runway into 2023 and has the ability to fully fund its Phase 1b/2a clinical trial of SYN-004 and planned Phase 1 SAD and MAD clinical trials of SYN-020;
Announced the appointment of senior biotech executive John Monahan, PhD, to the Company’s Board of Directors
Dr. Monahan brings to the Company more than 45 years of executive leadership experience in the pharmaceutical and biotechnologies industries.
Year Ended December 31, 2020 Financial Results

General and administrative expenses increased to $5.0 million for the year ended December 31, 2020, from $4.6 million for the year ended December 31, 2019. This increase of 8.7% is due to increased legal costs related to business development, patent execution, employee contract matters, vacation expense, insurance costs and registration fees. The charge relating to stock-based compensation expense was $300,000 for the year ended December 31, 2020, compared to $300,000 for the year ended December 31, 2019.

Research and development expenses decreased to $5.1 million for the year ended December 31, 2020, from $11.1 million for the year ended December 31, 2019. This decrease of 54.1% is primarily due to a reduction in preclinical and manufacturing activity of SYN-020 IAP and the result of the response to the global COVID-19 pandemic by our clinical development partners which led to the postponement of the Phase 1b/2a clinical trial of SYN-004 (ribaxamase) in allogeneic HCT recipients and the SYN-010 clinical trial and to a lesser extent the discontinuation of the Phase 2b investigator sponsored clinical trial of SYN-010. Research and development expenses also include a charge relating to non-cash stock-based compensation expense of $66,000 for the year ended December 31, 2020, compared to $75,000 for the year ended December 31, 2019.

Total other income was $44,000 for the year ended December 31, 2020, compared to other income of $283,000 for the year ended December 31, 2019. Total other income for the year ended December 31, 2020 and 2019 is primarily comprised of interest income from investments.

Cash and cash equivalents on December 31, 2020 were $6.2 million, a decrease of $8.8 million from December 31, 2019.

Conference Call

Synthetic Biologics will hold a conference call today, Thursday, March 4, 2021, at 4:30 p.m. (EST). The dial-in information for the call is as follows, U.S. toll free: 1-888-347-5280 or International: +1 412-902-4280. Participants are asked to dial in 15 minutes before the start of the call to register. The call will also be webcast over the Internet at View Source." target="_blank" title="View Source." rel="nofollow">View Source An archive of the call will be available for replay at the same URL, View Source, for 90 days after the call.

On March 4, 2021 NANOBIOTIX (Euronext : NANO –– NASDAQ: NBTX – the ‘‘Company’’), a clinical-stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported that the Company has reached an agreement with PharmaEngine, Inc. ("PharmaEngine") to terminate the License and Collaboration agreement that the Company and PharmaEngine entered into in August 2012 (Press release, Nanobiotix, MAR 4, 2021, View Source [SID1234576122]).

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As previously disclosed in the Nanobiotix prospectus filed with the U.S. Securities and Exchange Commission on December 11, 2020, in November 2020, Nanobiotix notified PharmaEngine of a material breach of the terms of the License and Collaboration agreement. In a letter dated December 1, 2020, PharmaEngine responded to the Company’s notification of material breach, denying a material breach of the License and Collaboration agreement, and asserting certain material breaches of that agreement by Nanobiotix. After discussion between the two parties, this agreement to terminate the License and Collaboration agreement represents a full resolution of outstanding disagreements over a number of issues with respect to the development of NBTXR3 in the Asia-Pacific region.

The License and Collaboration agreement provided PharmaEngine exclusive rights to further the development of NBTXR3 in the Asia-Pacific region. While both Nanobiotix and PharmaEngine believe in the potential of NBTXR3 to improve treatment outcomes for patients with cancer, the parties have had disagreements regarding the optimal strategy for development in the Asia-Pacific region. As such, Nanobiotix and PharmaEngine have mutually agreed to discontinue the collaboration.

Pursuant to their Termination and Release agreement, Nanobiotix will retain all rights to the development and commercialization of NBTXR3 in the Asia-Pacific region. PharmaEngine is to receive payments, not to exceed $5 million in total, upon the completion of various administrative steps in connection with the winding-up of the collaboration.

In the future, PharmaEngine will be entitled to receive a payment of $7.5 million upon a second regulatory approval of NBTXR3 in any jurisdiction of the world for any indication, unless the Company announces a collaboration with a new partner for the Asia-Pacific region within 6 months of the effective date of the agreement. If that occurs, PharmaEngine will be entitled to an immediate $2.5 million payment and will be eligible to receive a payment of the remaining $5 million upon such second regulatory approval of an NBTXR3-containing product. The Company has also agreed to pay royalties to PharmaEngine at low-single digit royalty rates with respect to sales of NBTXR3 in the Asia-Pacific region for a 10-year period commencing on the corresponding first date of sales in the region.

Retention of all rights regarding NBTXR3 will open new near- and long-term possibilities for the Company, and Nanobiotix will evaluate the Asia-Pacific region for potential inclusion in its upcoming global phase III registration trial in head and neck cancer.

About NBTXR3

NBTXR3 is a first-in-class radioenhancer composed of sterile, functionalized, crystalline hafnium oxide nanoparticles. The product candidate is designed to increase the radiotherapy energy deposit inside tumor cells through the nanoparticles’ high atomic number core packaged in the space for interaction with ionizing radiation, and subsequently increase of tumor cell death when compared to radiotherapy alone—without adding toxicity to adjacent healthy tissues. NBTXR3 requires a single, intratumoral administration before the first radiotherapy treatment session, and has the ability to fit into current worldwide standards of radiation care. The primary physical mechanism of action of NBTXR3 activated by radiotherapy could be universal, making it potentially applicable across any solid tumor indication where radiotherapy is a part of standard of care including head and neck, lung, prostate, liver, colorectal, and esophageal cancers. The biological secondary mechanism of action of NBTXR3 activated by radiotherapy has been shown in preclinical studies to prime adaptive immune response, which would potentially bring a new dimension to cancer immunotherapies.

On March 4, 2021 Genetron Holdings Limited ("Genetron Health" or the "Company", NASDAQ:GTH), a leading precision oncology platform company in China that specializes in offering molecular profiling tests, early cancer screening products and companion diagnostics development, reported that it will report unaudited financial results for the fourth quarter and full year ended December 31, 2020 on March 25, 2021 before the US market open (Press release, Genetron Health Technologies, MAR 4, 2021, View Source [SID1234576121]).

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Management will host a conference call for investors at 8:30 a.m. ET (8:30 p.m. Beijing time) on Thursday, March 25, 2021. The conference call can be accessed by dialing the following numbers:

Participants are encouraged to dial into the call at least 15 minutes in advance due to high call volumes.

A replay will be accessible through April 2, 2021 by dialing the following numbers:

A simultaneous webcast of the conference call will be available on the "News and Events" page of the Investors section of the Company’s website. A replay of the webcast will be available for 30 days following the event. For more information, please visit ir.genetronhealth.com.

On March 4, 2021 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that Alan H. Auerbach, Chairman, Chief Executive Officer, President and Founder of Puma, will provide an overview of the Company at the Barclays Global Healthcare Conference, which will be held virtually from March 9-11, 2021 (Press release, Puma Biotechnology, MAR 4, 2021, View Source [SID1234576120]). Puma’s presentation will take place at 1:50 p.m. EST (10:50 a.m. PST) on Thursday, March 11, 2021.

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A live webcast of the presentation will be available on the Company’s website at www.pumabiotechnology.com. The presentation will be archived on the website and available for 30 days.

On March 4, 2021 UNC Lineberger Comprehensive Cancer Center researchers reported that have successfully used an experimental safety switch, incorporated as part of a chimeric antigen receptor T-cell (CAR-T) therapy, a type of immunotherapy, to reduce the severity of treatment side effects that sometimes occur (Press release, Lineberger Comprehensive Cancer Center, MAR 4, 2021, View Source [SID1234576119]). This advance was seen in a patient enrolled in a clinical trial using CAR-T to treat refractory acute B-cell leukemia. It demonstrates a proof-of-principle for possible expanded use of CAR-T immunotherapy paired with the safety switch.

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The researchers published their findings in the journal Blood as an ahead-of-print publication.

With CAR-T therapy, T-cells from a patient’s immune system are modified in a manufacturing facility to express part of an antibody that can bind to a surface protein on cancer cells. The modified T-cells, after being infused back into the patient, seek out and attack cancer cells throughout the body. Patients with leukemia or lymphoma have experienced complete remission when treated with CAR-T therapy but sometimes experience toxicities, which can be life-threatening, due to inflammatory responses or nervous system toxicities caused by the modified T-cells.

When using standard forms of cancer therapies, including pills and infused drugs, doctors can interrupt or lower drug dosing to respond to treatment toxicities. With cell-based immunotherapies, this is not possible after the cells are infused. So UNC Lineberger researchers engineered T-cells to include a safety switch, called inducible caspase-9, or iC9, that can be activated if toxic side effects develop. Administration of the drug rimiducid "triggers" the switch to activate the expression of caspase-9, potentially leading to reduced severe side effects from the CAR-T therapy.

"Because of our active Cellular Immunotherapy Program at UNC Lineberger, we can engineer and generate various CAR-T cells for clinical trials. In this case, we have produced specialized CAR-T cells that could benefit patients by enhancing safety," said Matthew Foster, MD, lead author of the study and an associate professor in the UNC School of Medicine and a UNC Lineberger member. "With the assistance of our partner Bellicum Pharmaceuticals, we collaborated to use the safety switch-triggering drug rimiducid with cells manufactured at UNC Lineberger."

UNC Lineberger has enrolled patients in an ongoing early-phase clinical trial to determine whether a novel CAR-T therapy with the iC9 safety switch is safe and effective against relapsed or refractory B-cell acute lymphoblastic leukemia, a difficult to treat, fast-moving cancer that occurs frequently in children, adolescents and young adults.

One of the participants in the study, a 26-year-old woman, experienced a severe side effect — immune effector cell-associated neurotoxicity syndrome (ICANS) — after being infused with CAR-T. Her clinicians quickly reduced the severity of the side effects by administering the drug rimiducid to activate the iC9 safety switch. As intended, Foster said the safety switch reduced the number of circulating modified T-cells by nearly 60 percent within four hours and by more than 90 percent within 24 hours. The drug nearly eliminated the toxicities within one day.

"Even though this case study only documents an outcome in one patient, the fact that the drug was so successful so quickly gives us hope that it could have wider applications in a larger group of leukemia patients," said Gianpietro Dotti, MD, director of the UNC Lineberger Cellular Immunotherapy Program and professor of medicine at the UNC School of Medicine. "It should be noted that while rimiducid mitigated her toxicities, it also lowered the number of iC9 T cells fighting her cancer by 90 percent. But there seemed to be sufficient T-cells still circulating to maintain an anticancer response."

This trial is ongoing but the investigators will next explore the effects of lower doses of rimiducid in patients with less severe toxicity as it could be a way to intervene early and prevent severe toxicity.

"Given these results and the well-established high response rates in B-cell acute lymphoblastic leukemia patients receiving CAR-T cells, it is reasonable to have a high bar in 2021 and expect that we can achieve both safety and efficacy from such therapies," concluded Foster.

The investigators also see the potential to use CAR-T designed with the built-in safety switch to treat other cancers. "The ability to use a safety switch may also allow us to treat patients with solid tumors where there may be concern about the CAR-T cells affecting non-cancer tissue," said Jonathan Serody, MD, director of the UNC Lineberger Cellular Therapy Program. "In those instances, side effects can be eliminated by activating the safety switch."