On March 4, 2021 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported that it has executed an agreement with the Company’s largest shareholder, John K. Scott, Jr., to purchase $5 million of newly-designated Series E Redeemable Convertible Preferred Stock (Press release, Navidea Biopharmaceuticals, MAR 4, 2021, View Source [SID1234576087]). Over the next 18 months, the Series E Preferred can be converted into approximately 2.17 million shares of Navidea’s common stock.

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"We are pleased to receive continued support from our largest shareholder. Today’s financing provides additional strength to our balance sheet and will allow our company to accelerate potential value-accretive investments, including our therapeutics pipeline," commented Jed Latkin, Chief Executive Officer of Navidea. "We look forward to providing additional updates on the progress of our ongoing studies across our portfolio on our earnings call later this month."

John K. Scott, Jr. commented, "I am pleased to be given the opportunity to continue to support Navidea as it moves some of its key assets into the next phase of development. As a stockholder in Navidea since December 2003, I believe in the Company’s drug candidates and the positive contributions they can make to individuals and the scientific community."

The securities offered and to be sold by Navidea in the private placement to Mr. Scott have not been registered under the Securities Act of 1933 (the "Securities Act"), as amended, or state securities laws and may not be offered or sold in the United States absent registration with the Securities and Exchange Commission (the "SEC") or an applicable exemption from registration requirements. Navidea has agreed to file a registration statement with the SEC covering the resale of the shares of common stock to be issued to Mr. Scott.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of Navidea’s securities. No offer, solicitation or sale will be made in any state or other jurisdiction in which such offering, solicitation or sale would be unlawful.

On March 4, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX) reported that Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, will present at the H.C. Wainwright Global Life Sciences Conference, being held virtually March 9 – 10, 2021 (Press release, TG Therapeutics, MAR 4, 2021, View Source [SID1234576103]). The presentation will be accessible for on-demand download beginning on Tuesday, March 9, 2021 at 7:00 AM ET.

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A replay of this presentation will be available on the Events page, located within the Investors & Media section, of the Company’s website at View Source

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."

On March 4, 2021 ALX Oncology Holdings Inc. ("ALX Oncology") (Nasdaq: ALXO), a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, and Tallac Therapeutics, Inc. ("Tallac"), a privately held biopharmaceutical company harnessing the power of innate and adaptive immunity to fight cancer, reported a collaboration to jointly develop, manufacture, and commercialize a novel class of cancer immunotherapeutics (Press release, Tallac Therapeutics, MAR 4, 2021, View Source [SID1234579742]). Under the terms of the agreement, ALX Oncology and Tallac will share equally in the cost of research and development and any profits or losses incurred.

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The collaboration builds on ALX Oncology’s expertise in developing therapies that block the CD47 checkpoint pathway and expands its immuno-oncology pipeline. The collaboration also extends Tallac’s pipeline of next generation immunotherapies derived from its novel Toll-like Receptor Agonist Antibody Conjugate ("TRAAC") platform. The companies will leverage their respective scientific and technical expertise to advance an anti-SIRPα antibody conjugated to a Toll-like receptor 9 ("TLR9") agonist for targeted activation of both the innate and adaptive immune systems.

"We are excited to partner with ALX Oncology in the development of next-generation breakthrough cancer immunotherapies," said Hong I. Wan, Ph.D., President, Chief Executive Officer and co-founder of Tallac. "TLR9 agonists are a class of immunotherapy that generate both innate and adaptive immune responses which may produce robust and durable anti-cancer immunity for patients with advanced-stage cancers. While intratumoral TLR9 agonists have clinically validated this pathway, systemic administration has been unsuccessful, limiting clinical utility in broader patient populations. With Tallac’s TRAAC technology, we now have a way to target this pathway systemically, which could expand the clinical benefit to a much broader patient population. To date, we have generated promising preclinical data with multiple TRAAC molecules that demonstrates the potential of this pathway. The goal of our collaboration with ALX Oncology is to advance SIRPα TRAAC, a systemically delivered TLR9 agonist targeting dendritic cells via SIRPα receptors, enabling a powerful innate and adaptive anti-tumor immune response."

"Collaborating with Tallac and their novel TRAAC platform broadens ALX Oncology’s therapeutic strategies to activate the innate immune system and SIRPα TRAAC complements our lead product candidate, ALX148," said Jaume Pons, Ph.D., Founder, President and Chief Executive Officer of ALX Oncology. "While ALX148 is an antagonistic molecule designed to maximize the activity of a wide array of anticancer agents by the blockade of the CD47 myeloid checkpoint, SIRPα TRAAC is an agonistic molecule that directly activates dendritic cells and enables a coordinated innate and adaptive immune response against cancer. Since SIRPα is expressed on both dendritic cells and a range of tumor types, SIRPα TRAAC may enable an effective immune activation response in advanced cancer settings. We are excited about this potentially transformative approach and the possible benefits to patients that are in need of new treatment options."

Conference Call on March 5 at 8:30 a.m. EST

ALX Oncology and Tallac will host a conference call on Friday, March 5, 2021 at 8:30 a.m. EST to further discuss the collaboration.

To access the conference call, please dial (844) 467-7655 (local) or (409) 983-9840 (international) at least 10 minutes prior to the start time and refer to conference ID 4117088. Presentation slides will be available to download under "News & Events" (see "Events") in the investors section of the ALX Oncology website at www.alxoncology.com.

On March 4, 2021 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a leader in the discovery and development of novel therapies targeting diseases resulting from dysfunction of the CXCR4 pathway, reported financial results for the fourth quarter and full year ended December 31, 2020 (Press release, X4 Pharmaceuticals, MAR 4, 2021, View Source [SID1234576072]). The company also provided an update on its lead product candidate, mavorixafor, a novel small molecule currently being evaluated in a Phase 3 clinical trial (4WHIM) for patients with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome and in two Phase 1b trials for patients with Waldenström’s macroglobulinemia (Waldenström’s) and Severe Congenital Neutropenia (SCN), respectively.

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"As many companies did, we encountered a number of unexpected challenges in 2020, most notably the COVID-19 pandemic. However, I could not be prouder of our accomplishments, as we remained steadfast in our commitment to advance our lead candidate, mavorixafor, in a number of rare disease indications," said Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. "We believe that we have much to look forward to this year, as we have overcome these obstacles, have made significant progress in advancing our clinical and research programs, and assembled an exceptional team to execute on our 2021 goals and beyond.

"On the clinical front, we continue to expect top-line data from our Phase 3 WHIM trial in 2022 and, as our Phase 1b Waldenström’s trial is progressing well, we continue to expect initial data from that study in the first half of 2021, with a more fulsome dataset expected towards the end of 2021. We also anticipate initial data from our SCN Phase 1b trial in 2021."

Recent Highlights

Received Fast Track and Rare Pediatric Designations (RPD) from the FDA for Mavorixafor for the treatment of WHIM Syndrome: These FDA designations further recognize WHIM as a serious condition with a clear unmet need in both adult and pediatric populations.
Through the Fast Track program, X4 will be eligible for more frequent meetings with the FDA to discuss the drug’s development plan, protocols and clinical data that would support mavorixafor’s potential approval for WHIM.
Under the RPD program, a sponsor who receives an approval for a drug for a "rare pediatric disease" and a Fast Track designation may qualify for a voucher that can be redeemed to receive a priority review by the FDA for any subsequent marketing application for a different product. Such a voucher is transferable and may be sold.
Mavorixafor was previously granted Breakthrough Therapy Designation by the FDA, as well as Orphan Drug status by the FDA and the European Commission for the treatment of WHIM syndrome.
Strengthened Leadership Team: During the Fourth Quarter of 2020:
Diego Cadavid, M.D., joined as Chief Medical Officer, bringing more than 20 years of industry experience and having led multiple programs through all phases of clinical development, including small molecules and biologics for the treatment of rare and immunological diseases.
Art Taveras, Ph.D., joined as Chief Scientific Officer with more than 30 years of experience leading small molecule research and development programs focused on cancer, dysregulated immune disorders, neurodegeneration, and metabolic diseases.
Alison Lawton was appointed to the company’s Board of Directors, bringing more than 30 years of experience across a full spectrum of drug development and commercial roles and having previously served on X4’s corporate advisory board and as consulting Chief Operating Officer.
Fourth Quarter 2020 Financial Results

Cash, Cash Equivalents & Restricted Cash: X4 had $80.7 million in cash, cash equivalents and restricted cash as of December 31, 2020. X4 continues to expect that its cash and cash equivalents will fund company operations into 2022.
Research and Development Expenses were $12.3 million and $41.9 million for the fourth quarter and full year ended December 31, 2020, respectively, as compared to $7.1 million and $30.2 million for the comparable periods in 2019, respectively. R&D expenses include $0.6 million and $2.3 million of certain non-cash expenses for the fourth quarter and fully year ended December 31, 2020, respectively.
General and Administrative Expenses were $5.4 million and $20.9 million for the fourth quarter and full year ended December 31, 2020, respectively, as compared to $3.9 million and $17.6 million for the comparable periods in 2019, respectively. G&A expenses include $0.8 million and $3.1 million of certain non-cash expenses for the fourth quarter and full year ended December 31, 2020, respectively.
Net Loss: X4 reported net losses of $18.4 million and $62.1 million for the fourth quarter and full year ended December 31, 2020 as compared to net losses of $10.8 million and $52.8 million for the comparable periods in 2019, respectively. Net losses include $1.4 million and $5.4 million of certain non-cash expenses for the fourth quarter and full year ended December 31, 2020, respectively. Net losses in the full year of 2019 included a $3.9 million loss on the sale of non-financial assets.
Conference Call and Webcast
The Company will host a conference call and webcast today at 8:30 a.m. ET to discuss these financial results and business highlights. The conference call can be accessed by dialing (866) 721-7655 from the United States or (409) 216-0009 internationally, followed by the conference ID: 1053189. The live webcast can be accessed on the investor relations section of X4 Pharmaceuticals’ website at www.x4pharma.com. Following the completion of the call, a webcast replay of the conference call will be available on the website.