On November 19, 2021, Xenetic Biosciences, Inc. (the "Company") reported that entered into an At The Market Offering Agreement (the "ATM Agreement") with H.C. Wainwright & Co., LLC, as the exclusive sales agent ("Wainwright"), pursuant to which the Company may offer and sell, from time to time through Wainwright, shares (the "Shares") of its common stock, par value $0.001 per share ("Common Stock") (Filing, 8-K, Xenetic Biosciences, NOV 19, 2021, View Source [SID1234595845]). The offer and sale of the Shares will be made pursuant to a shelf registration statement on Form S-3 (File No. 333-260201) and the related prospectus, as supplemented by a prospectus supplement dated November 19, 2021 (the "Prospectus Supplement") and filed with the Securities and Exchange Commission (the "SEC") on such date pursuant to Rule 424(b) under the Securities Act of 1933, as amended (the "Securities Act"), and is currently limited to a number of Shares of up to $4,000,000 of Common Stock pursuant to General Instruction I.B.6 of Form S-3.

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Pursuant to the ATM Agreement, Wainwright may sell the Shares in sales deemed to be "at-the-market" equity offerings as defined in Rule 415 promulgated under the Securities Act, including sales made directly on or through the Nasdaq Capital Market. If agreed to in a separate terms agreement, the Company may sell Shares to Wainwright as principal, at a purchase price agreed upon by Wainwright and the Company. Wainwright may also sell Shares in privately negotiated transactions with the Company’s prior approval. Sales of the Shares through Wainwright, if any, will be made in amounts and at times to be determined by the Company from time to time, but the Company has no obligation to sell any of the Shares and either the Company or Wainwright may at any time suspend offers under the Agreement or terminate the Agreement. Actual sales will depend on a variety of factors to be determined by the Company from time to time, including (among others) market conditions, the trading price of the Company’s common stock and determinations by the Company of the appropriate sources of funding for the Company. The offer and sale of the Shares pursuant to the ATM Agreement will terminate upon the earlier of (a) the issuance and sale of all of the Shares subject to the ATM Agreement or (b) the termination of the ATM Agreement by Wainwright or the Company pursuant to the terms thereof.

The Sales Agreement provides that Wainwright will be entitled to compensation of up to 3.0% of the gross sales price of any Shares sold by Wainwright under the Sales Agreement. The Company also will reimburse Wainwright for certain specified expenses in connection with entering into the ATM Agreement. The Company has agreed to provide Wainwright with customary indemnification and contribution rights, including for liabilities under the Securities Act. The ATM Agreement contains customary representations and warranties and conditions to the placements of the Shares pursuant thereto.

A copy of the ATM Agreement is filed as Exhibit 1.1 to this Current Report on Form 8-K, and the description of the terms of the ATM Agreement is qualified in its entirety by reference to such exhibit. A copy of the opinion of Westward Law LLC relating to the legality of the issuance and sale of the Shares is attached as Exhibit 5.1 hereto.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the Shares, nor shall there be any offer, solicitation, or sale of the Shares in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

On November 19, 2021 Tempus, a leader in artificial intelligence and precision medicine, reported a multi-year, strategic collaboration with AstraZeneca (LSE/STO/Nasdaq: AZN) in which the two companies will work together to gather insights, discover novel drug targets, and aim to develop therapeutics for the broader oncology community (Press release, Tempus, NOV 19, 2021, View Source [SID1234595857]). By combining the capabilities of a technology company with those of a biopharmaceutical company, the two companies hope to advance drug discovery and development, to more quickly deliver innovation to patients.

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We are very pleased to collaborate with Tempus to enhance our data-driven R&D strategy and glean critical insights that will deepen our understanding of complex tumor biology, enhance access to predictive preclinical models, and increase the probability of clinical success across our diverse pipeline.

Artificial intelligence has the potential to advance precision medicine in ways that seemed unimaginable just a few short years ago," said Eric Lefkofsky, Founder and CEO of Tempus. "We look forward to working with AstraZeneca to apply AI-enabled solutions to advance its robust therapeutic pipeline in an effort to help patients live longer and healthier lives."

Cancer drug discovery and clinical development are being transformed by the ability to analyze vast amounts of rich data using artificial intelligence," said Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca. "We are very pleased to collaborate with Tempus to enhance our data-driven R&D strategy and glean critical insights that will deepen our understanding of complex tumor biology, enhance access to predictive preclinical models, and increase the probability of clinical success across our diverse pipeline.

On November 16, 2021 Bright Peak Therapeutics, Inc., a biotechnology company developing next-generation cytokine immunotherapies, reported that it has entered into a license agreement with Livzon Mabpharm, Inc. ("Livzon"), a subsidiary company of Livzon Pharmaceutical Group, to use LZM009, Livzon’s proprietary anti-PD-1 monoclonal antibody currently in late-stage clinical trials, to develop novel PD-1 targeted immunocytokines ("PD-1 ICs") (Press release, Livzon Pharmaceutical Group, NOV 19, 2021, View Source [SID1234595846]). The PD-1 ICs will be comprised of optimized cytokine payloads developed by Bright Peak conjugated to LZM009 for the treatment of a variety of cancers. PD-1 ICs are designed to selectively target and activate cytotoxic CD8+ T cells ("CTLs") that express the inhibitory immune checkpoint PD-1 while avoiding the broad activation of other immune cells. Dual targeting of two receptors on the same CTL with a PD-1 inhibitor and a cytokine payload (cis-signaling) offers the added potential for synergistic efficacy.

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Bright Peak is dedicated to creating next-generation immunotherapies that exploit the potent biological activity of cytokines while showing a significantly improved safety profile. Using Bright Peak’s unique chemical protein synthesis and engineering platform, cytokines can be precisely designed to fine-tune receptor binding, optimize efficacy, and simultaneously insert conjugation handles at any desired site in a protein. This allows for rapid conjugation of enhanced cytokines as payloads to commonly used antibodies, creating novel and proprietary "Bright Peak Immunocytokines." One of the many advantages of Bright Peak’s technology is the ‘off-the-shelf’ ability to convert existing therapeutic antibodies into dual-targeting immunocytokines by a simple and rapid chemical process. The platform also readily enables the screening of various cytokine payloads with differential properties to elicit the desired biological effects. Moreover, Bright Peak’s approach allows the use of antibodies ‘as-is,’ avoiding the complex process of generating recombinant antibody-cytokine fusion proteins which involves lengthy protein expression, optimization and cell-line development.

"We are delighted to license Livzon’s anti-PD-1 monoclonal antibody LZM009 to broadly develop PD-1 directed immunocytokines by leveraging our proprietary platform technology," said Fredrik Wiklund, President and Chief Executive Officer of Bright Peak. "PD-1 inhibitors have changed the landscape of cancer therapy in recent years. However, despite the remarkable efficacy observed in a subset of patients treated with PD-1 inhibitors, most patients do not respond. Bright Peak’s PD-1 ICs have the potential to enhance the activity of PD-1 inhibition to bring the promise of immunotherapy to a greater number of patients."

"We are excited to apply the power and versatility of our synthetic protein engineering platform to generate PD-1 ICs by conjugating optimized cytokine payloads to a clinical stage antibody. PD-1 ICs are designed to utilize the concept of cis-signaling cytokines acting on the same cell that is targeted by the anti-PD-1 antibody. As a result, they are more potent and selective and have an increased capacity to induce superior CD8+ T cell responses," said Bertolt Kreft, Ph.D., Chief Scientific Officer of Bright Peak.

"Livzon’s PD-1 molecule has proprietary patents with broad application potential, and we are very happy to enter into an agreement with Bright Peak who possesses an innovative conjugation and protein engineering technology platform to explore and achieve dual-targeting effects of novel molecules to benefit patients with unmet medical needs," said Jianing Liu, Ph.D., Chief Investment Officer and Head of BD of Livzon Pharmaceutical Group. "Livzon Mabpharm is more than happy to support innovative global R&D with inspiring partners leveraging on our existing pipelines and experience in biologics, and we believe this is one step further to demonstrate Livzon MabPharm’s capabilities and readiness for global outreach," said Jiaming Yang, Ph.D., Executive Vice President of Livzon Mabpharm, Inc.

Under the terms of the license agreement, Bright Peak will receive the right to develop, manufacture and commercialize PD-1 ICs on a worldwide basis while Livzon retains certain rights of first negotiation to obtain exclusivity in the greater China territory. Livzon will receive a one-time upfront cash payment from Bright Peak and is eligible to receive additional cash payments upon the achievement of future development and regulatory milestones, as well as royalties in the low-to-mid single digit percentage range on worldwide net sales. Bright Peak will solely control and fund all activities related to development and commercialization on a worldwide basis, subject to Livzon’s right of first negotiation in greater China.

About LZM009
LZM009 is a human IgG4 monoclonal antibody which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1/ PD-Ligand 1 (PD-L1) pathway and reactivates T cells to kill cancer cells. LZM009 has been approved for clinical trials and completed clinical dose exploration trials in both China and the United States. LZM009 is undergoing extensive clinical trials, including pivotal trials in thymic cancer in China, with promising initial safety and efficacy data.

On November 18, 2021 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a U.S. clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, reported that positive interim data on its lead investigational drug, Rhenium-186 NanoLiposome (186RNL), from the first-in-man Phase 1 ReSPECT-GBM clinical trial in patients with recurrent glioblastoma (GBM) at the 2021 Society for Neuro-Oncology Annual Meeting and Education Day being held in Boston, Massachusetts (Press release, Cytori Therapeutics, NOV 18, 2021, View Source [SID1234595776]).

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According to the interim data, 186RNL delivered via convection enhanced delivery (CED) is well-tolerated with favorable overall survival in adult patients at higher absorbed radiation doses (greater than 100 Gy). A positive correlation was observed between overall survival and higher absorbed radiation doses (greater than 100 Gy).

The poster, titled "Safety and Feasibility of Rhenium-186 NanoLiposome (186RNL) in Recurrent Glioma: the ReSPECT Phase 1 Trial," outlines data from the ReSPECTTM-GBM trial, substantially funded by the U.S. National Institutes of Health/National Cancer Institute, which has thus far evaluated 22 adult patients with recurrent GBM across seven cohorts of increasing dose, treated over a six year period.

"In the ReSPECTTM trial thus far, 186RNL has been well-tolerated without dose-limiting toxicities and we believe further clinical investigation of relative efficacy is warranted," said Andrew J. Brenner, M.D., Ph.D., Professor of Medicine, Neurology, and Neurosurgery at The University of Texas Health Science Center at San Antonio and principal investigator of the ReSPECT-GBM clinical trial. "The open label, dose escalation trial was not designed to show efficacy but the trends observed between overall survival and key delivery parameters such as therapeutic radiation dose to the tumor are promising."

Key findings include the following:

No delivery failures were observed and an average absorbed dose of 267.5 Gy (range 8.9-740Gy) of radiation was delivered to the tumor.
No dose limiting toxicities or adverse events (AEs) with the outcome of death, or discontinuations due to AEs have been observed.
Of 22 total subjects with recurrent GBM treated with 186RNL, seven patients remain alive and mean and median overall survival (OS) is currently 336.6 days and 231.5 days, respectively.
In the subset of 13 patients receiving greater than 100 Gy absorbed radiation, seven patients remain alive and mean and median OS is currently at 453.8 days and 330 days respectively.
No patients remain alive in the cohort of 9 patients receiving less than 100 Gy absorbed radiation and mean and median OS is 167.3 days and 156 days respectively.
In 10 treated patients in cohorts five through seven, 13.4 millicuries or more of radiation was delivered and 80% received greater than 100 Gy average absorbed dose of radiation to the tumor.
"Our team is pleased with the clinical performance and the potential promise of 186RNL in patients with this devastating disease," said Marc Hedrick, M.D., President and Chief Executive Officer of Plus Therapeutics. "In particular, the observation that we may be able to reliably and precisely deliver a significant therapeutic dose of radiation greater than 100 Gy and potentially influence survival is a positive development. We look forward to completing key drug scale-up activities and proceed to FDA discussions regarding CMC and next clinical steps in early 2022."

For a more detailed discussion of the ReSPECT-GBM trial data, please join the Plus Therapeutics hosted webinar on Thursday, November 18, 2021, 4:00 to 5:00 p.m. ET (details below).

A copy of the poster will be available under the Presentations tab of the Investors section of the Company’s website at View Source

Key Opinion Leader Roundtable Webinar Details

A live webinar with accompanying slides will be available in the Events page of the Investor Relations section of the Plus Therapeutics website. Individuals can participate in an interactive Q&A session by submitting pertinent questions via the webcast platform.

Please log in approximately 10 minutes prior to the scheduled start time of 4:00 p.m. ET on November 18, 2021. The archived webcast will be available in the Events section of the Company’s website for 90 days.

A live audio conference will be available by dialing (833) 340-0285 (toll-free) or (236) 712-2475 and entering Conference ID 3170796.

About Rhenium-186 NanoLiposome

Rhenium-186 NanoLiposome (186RNL) is under investigation as a potentially safe, effective and convenient way to deliver a very high dose of radiation, possibly over 20 times greater than traditional external beam radiation therapy. This trial is supported by the U.S. National Institutes of Health/National Cancer Institute at three trial sites in the U.S., including UT Health Science Center San Antonio, UT Southwestern Medical Center Dallas and UT MD Anderson Cancer Center Houston.

The U.S. Food and Drug Administration has granted both Orphan Drug designation and Fast Track designation to 186RNL for the treatment of patients with GBM. Additional details about the ReSPECT trial are available at clinicaltrials.gov (NCT01906385).

On November 18, 2021 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a late clinical-stage biopharmaceutical company focused on oncology, reported its financial results for the quarter ended September 30, 2021 and provides a corporate update (Press release, BioLineRx, NOV 18, 2021, View Source [SID1234595792]).

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Significant events and achievements during the third quarter 2021 and subsequent period:

Announced statistically significant positive results from a pharmacoeconomic cost effectiveness study supporting Motixafortide’s use as the new standard-of-care and primary mobilization agent (in combination with G-CSF) in stem cell mobilization (SCM). The study demonstrated substantial clinical benefits and cost savings in favor of Motixafortide from a significantly higher number of mobilized cells, reduced numbers of apheresis sessions and reduced doses of G-CSF;
Announced acceptance of an oral presentation, as well as three poster presentations, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, which is taking place December 11-14. The presentations, which include an oral presentation describing the highly significant and clinically meaningful results from the Company’s GENESIS Phase 3 clinical trial in stem cell mobilization (SCM), reflect the versatility of Motixafortide as the backbone of promising new treatments for both hematological and solid tumor cancers;
Finalized preparations for a pre-NDA meeting with FDA, which is set for mid-December;
Proceeded with activities in support of a New Drug Application (NDA) submission in stem cell mobilization planned for the first half of 2022;
Ended the third quarter on a solid financial footing, with cash and cash equivalents of $62.2 million.
"The key highlight since our last quarterly update was the statistically significant positive results from a pharmacoeconomic study of Motixafortide in stem cell mobilization for multiple myeloma patients," stated Philip Serlin, Chief Executive Officer of BioLineRx. "The study demonstrated that use of Motixafortide on top of G-CSF resulted in a net cost savings of $17,000 per patient, not including the cost of Motixafortide, driven by fewer doses of G-CSF and a reduction in the number of apheresis sessions and related costs, versus G-CSF alone. These cost savings should leave substantial room in the future to optimize our pricing strategy for Motixafortide at product launch and thereafter, if approved.

"These results, together with the overwhelmingly positive results from our GENESIS Phase 3 study, which showed that almost 90% of patients collected an optimal number of cells for transplantation following a single administration of Motixafortide and in only one apheresis session, strongly support our view that Motixafortide, in combination with G-CSF, can become the new standard of care in SCM as an upfront, or primary, therapy for all multiple myeloma patients. If approved, this represents a significant advancement in SCM to the benefit of patients and payers alike and, to that end, we plan to submit an NDA to the FDA in the first half of next year.

"Our significant progress in SCM, together with the encouraging results we have seen in trials to date in metastatic pancreatic cancer, reflect the versatility of Motixafortide in both hematological and solid tumor cancers, which we have an opportunity to highlight at this year’s ASH (Free ASH Whitepaper) meeting next month. Our notable presence at such an important medical conference reflects the excellent progress that we have made to date across these core programs and underscores the momentum that we have entering 2022.

"With over $62 million in cash, we believe we are well financed to achieve our upcoming important and potentially value creating milestones," Mr. Serlin concluded.

Upcoming Expected Milestones:

Complete pre-NDA meeting with the FDA for SCM, scheduled for mid-December 2021;
Complete recruitment of part 2 of ongoing Phase 1/2a trial of AGI-134 in solid tumors by end of 2021;
Announce initial results for Part 2 of Phase 1/2a trial of AGI-134 in solid tumors in first half of 2022;
Submit NDA for Motixafortide in SCM in first half of 2022.
Financial Results for the Quarter Ended September 30, 2021

Research and development expenses for the three months ended September 30, 2021 were $4.9 million, an increase of $1.4 million, or 41.3%, compared to $3.5 million for the three months ended September 30, 2020. The increase resulted primarily from an increase in expenses associated with the AGI-134 study and a timing difference related to a tax credit received in respect of AGI-134, as well as an increase in payroll and related-expenses due to a company-wide salary reduction related to the COVID-19 pandemic in the comparable 2020 period. Research and development expenses for the nine months ended September 30, 2021 were $14.3 million, an increase of $0.8 million, or 5.9%, compared to $13.5 million for the nine months ended September 30, 2020. The increase resulted primarily from an increase in expenses associated with the AGI-134 study, as well as an increase in payroll and related-expenses due to a company-wide salary reduction related to the COVID-19 pandemic in the comparable 2020 period, offset by lower expenses associated with the completed Motixafortide GENESIS and COMBAT clinical trials.

Sales and marketing expenses for the three months ended September 30, 2021 were $0.2 million, a decrease of $0.1 million, or 20.1%, compared to $0.3 million for the three months ended September 30, 2020. The decrease resulted primarily from lower consultancy services related to Motixafortide. Sales and marketing expenses for the nine months ended September 30, 2021 were $0.7 million, similar to the comparable period in 2020.

General and administrative expenses for the three months ended September 30, 2021 were $1.1 million, an increase of $0.2 million, or 22.3%, compared to $0.9 million for the three months ended September 30, 2020. The increase resulted primarily from an increase in directors’ and officers’ insurance. General and administrative expenses for the nine months ended September 30, 2021 were $3.1 million, an increase of $0.3 million, or 9.3%, compared to $2.8 million for the nine months ended September 30, 2020. The reason for the increase is similar to the aforementioned increase in the three-month period.

The Company’s operating loss for the three months ended September 30, 2021 amounted to $6.2 million, compared to an operating loss of $4.6 million for the quarter ended September 30, 2020. The Company’s operating loss for the nine months ended September 30, 2021 was $18.2 million, compared to $17.1 million for the comparable period in 2020.

Non-operating income (expenses) for the three and nine months ended September 30, 2021 primarily relate to fair-value adjustments of warrant liabilities on the Company’s balance sheet and issuance expenses of the ATM. Non-operating income (expenses) for the three and nine months ended September 30, 2020 primarily relate to fair-value adjustments of warrant liabilities on the Company’s balance sheet, offset by warrant offering expenses and issuance expenses of the ATM.

Net financial expenses for the three months ended September 30, 2021 amounted to $0.2 million compared to net financial expenses of $0.3 million for the three months ended September 30, 2020. Net financial expenses for the nine months ended September 30, 2021 amounted to $0.5 million compared to net financial expenses of $0.9 million for the nine months ended September 30, 2020. Net financial expenses for all periods primarily relate to interest paid on loans, offset by investment income earned on bank deposits.

The Company’s net loss for the three months ended September 30, 2021 amounted to $5.7 million, compared with a net loss of $4.6 million for the comparable period in 2020. The Company’s net loss for the nine months ended September 30, 2021 amounted to $22.8 million, compared with a net loss of $18.0 million for the comparable period in 2020.

The Company held $62.2 million in cash, cash equivalents and short-term bank deposits as of September 30, 2021.

Net cash used in operating activities was $18.1 million for the nine months ended September 30, 2021, compared with net cash used in operating activities of $17.8 million for the nine months ended September 30, 2020. The $0.3 million increase in net cash used in operating activities in 2021 was primarily the result of an increase in research and development expenses.

Net cash used in investing activities was $42.2 million for the nine months ended September 30, 2021, compared to net cash provided by investing activities of $8.1 million for the nine months ended September 30, 2020. The changes in cash flows from investing activities relate primarily to investments in, and maturities of, short-term bank deposits.

Net cash provided by financing activities was $57.6 million for the nine months ended September 30, 2021, compared to net cash provided by financing activities of $10.9 million for the nine months ended September 30, 2020. The cash flows in 2021 primarily reflect the underwritten public offering of our ADSs in January 2021, warrant exercises, and net proceeds from the ATM facility, offset by repayments of the loan from Kreos Capital. The cash flows in 2020 primarily reflect two registered direct offerings to institutional investors, net proceeds from the ATM facility, offset by repayments of the loan from Kreos Capital.

Conference Call and Webcast Information

BioLineRx will hold a conference call today, Thursday, November 18, 2021, at 10:00 a.m. EST. To access the conference call, please dial +1-866-744-5399 from the US or +972-3-918-0644 internationally. The call will also be available via webcast and can be accessed through the Investor Relations page of BioLineRx’s website. Please allow extra time prior to the call to visit the site and download any necessary software to listen to the live broadcast.

A replay of the conference call will be available approximately two hours after completion of the live conference call on the Investor Relations page of BioLineRx’s website. A dial-in replay of the call will be available until November 21, 2021; please dial +1-888-295-2634 from the US or +972-3-925-5904 internationally.