On April 18, 2023 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a clinical-stage global biopharmaceutical company focused on using its novel technology platform for drug discovery and development of innovative therapies to improve clinical outcomes for patients with high unmet medical needs, reported a business update and provided results for the year ended December 31, 2022 (Press release, BeyondSpring Pharmaceuticals, APR 18, 2023, View Source;utm_medium=rss&utm_campaign=beyondspring-provides-business-update-and-reports-year-end-2022-financial-results [SID1234630230]).

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"I am pleased to report that BeyondSpring’s subsidiary, SEED Therapeutics, has made significant headway in advancing internal and external collaboration assets with Eli Lilly, achieving on-time delivery of R&D objectives, which triggered milestones and investment payments," said Dr. Lan Huang, Co-Founder, Chairman and CEO of BeyondSpring. "SEED Therapeutics, which specializes in ‘molecular glue’ development with its proprietary targeted protein degradation (TPD) platform for novel drug discovery, continues to attract increased partnering interest."

Dr. Huang continued, "BeyondSpring remains strategically positioned to advance our programs to near-term important inflection points. The Company continues to make progress in advancing our lead drug candidate, Plinabulin, as a ‘pipeline in a drug’ on the regulatory front in the U.S. and in China, and in a number of Plinabulin IIT studies at MD Anderson, Memorial Sloan Kettering and other institutions in the U.S. and China."

Recent Business and Clinical Updates

Business Updates

SEED Milestone Achievements
SEED Therapeutics received investment payment in June 2022 and milestone payment in February 2023 for pre-clinical development from Eli Lilly, totaling $7 million.

Plinabulin
In March 2023, BeyondSpring withdrew its NDA submission for the CIN indication from China’s National Medical Products Administration (NMPA) review. The Company will continue to communicate with the NMPA regarding its re-filing of the NDA for the CIN indication and plan to re-file the NDA by mid-2023. In addition, the Company plans to submit the NDA for the NSCLC indication with the NMPA by mid-2023.

Clinical Updates

Conference Presentations at ASH (Free ASH Whitepaper), SABCS, and ESMO (Free ESMO Whitepaper) Asia for Plinabulin
In December 2022, the Company exhibited two posters and gave one oral presentation on positive data with Plinabulin for the prevention of docetaxel-induced neutropenia (DIN) in patients with NSCLC and breast cancer at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Congress and San Antonio Breast Cancer Symposium (SABCS).
Enrollment Completion for Three IIT Studies in the U.S. for Plinabulin
In February 2023, the Phase 2 IIT study enrollment was completed for Plinabulin combined with Bristol Myers Squibb’s Opdivo and Yervoy in 2nd/3rd line extensive-stage small cell lung cancer (ES-SCLC) patients who had failed prior immunotherapy. In the Phase 1 IIT study, the preliminary data showed over 40% of tumor response in this population.
In March 2023, the Phase 1 IIT study enrollment was completed for Plinabulin, combined with PD-1 / PD-L1 inhibitors and radiation, in a variety of cancer patients who had failed prior immunotherapies at the MD Anderson Cancer Center.
In March 2023, the Phase 1 IIT study enrollment was completed for Plinabulin in combination with Pegfilgrastim in multiple myeloma (MM) patients who had undergone autologous hematopoietic cell transplantation (AHCT) at the Memorial Sloan Kettering Cancer Center (MSKCC). The topline data will be presented at the upcoming ASCO (Free ASCO Whitepaper) meeting in June 2023.

First Patient Enrollment in Phase 2 IIT Study for Plinabulin Combined with Keytruda and Docetaxel in 2nd/3rd line NSCLC
In March 2023, the first patient was enrolled in a Phase 2 IIT study for Plinabulin in combination with Merck’s anti-PD-1 therapy, Keytruda, and docetaxel for patients with metastatic NSCLC who had failed immunotherapy alone or in combination with platinum-doublet chemotherapy.
Expected Milestones in 2023

Advance a lead SEED-owned new chemical entity (NCE) to the IND-candidate milestone
Advance a second SEED-owned NCE to the Hit milestone with efficacy in animal model
Complete three IIT studies in the U.S. with Topline Data Readout
Plan to Submit NSCLC NDA in China by mid-2023
Plan to Re-submit CIN NDA in China by mid-2023
Full Year 2022 Financial Results

Research and development ("R&D") expenses were $25.6 million for the year ended December 31, 2022, compared to $36.9 million for the year ended December 30, 2021. The $11.3 million decrease was primarily due to lower clinical development expense, lower regulatory fees and professional service expense to support NDA submission and lower personnel costs as a result of the organizational streamlining announced in January 2022.

General and administrative ("G&A") expenses were $13.0 million for the year ended December 31, 2022, compared to $30.7 million for the year ended December 31, 2021. The $17.7 million decrease was primarily due to lower pre-commercialization expenses for Plinabulin and lower personnel costs, as results of the organizational streamlining announced in January 2022. There were also decreases in professional service expenses.

Net loss attributable to the Company was $33.3 million for the year ended December 31, 2022, compared to $64.2 million for the year ended December 31, 2021.

As of December 31, 2022, the Company had cash, cash equivalents, and short-term investments of $37.3 million.

On April 18, 2023 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported that it presented data linking AXL activation to STK11 loss of function in Non-Small Cell Lung Cancer (NSCLC) in an abstract titled, AXL as a Therapeutic Target in STK11 mutant NSCLC, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (Press release, BerGenBio, APR 18, 2023, View Source [SID1234630228]).

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An analysis of tumors lacking STK11 function from BerGenBio’s 2nd line NSCLC trial (BGBC008) and publicly available datasets suggest that STK11 and KEAP1 mutations are transcriptionally similar and share a common signature for STK11 loss of function. Loss of function leading to inactivation of STK11 is found in approximately 30% of lung adenocarcinomas as a result of both mutational and non-mutational mechanisms. These tumors with inactivated STK11 are likely to promote AXL activation due to high levels of energetic and metabolic stress, resulting in a poorer prognosis in NSCLC.

AXL, a member of the TAM family of receptor tyrosine kinases, is expressed in over 80% of NSCLC tumors that demonstrate loss of STK11 function. AXL is activated in response to inflammation, hypoxia, cellular stress or drug treatment. AXL is expressed in both tumor cells, where it enhances survival and drug resistance, and in innate immune cells, such as dendritic cells and macrophages, where AXL drives immune suppression. BerGenBio’s selective AXL inhibitor bemcentinib targets key survival and resistance mechanisms within the tumor and restores the anti-tumor characteristics of innate immune cells within the tumor microenvironment.

"There is accumulating evidence substantiating the importance of targeting AXL within the tumor and innate immune cells of the tumor microenvironment," said Nigel McCracken,Ph.D., Chief Scientific Officer of BerGenBio. "A loss of STK11 function due to STK11 or KEAP1 mutations is associated with a poorer prognosis, irrespective of treatment modality and represents a large subgroup of NSCLC patients with high unmet need. Our preclinical data and the clinical data from our Phase 2 trial evaluating bemcentinib in combination with pembrolizumab support targeting AXL in both STK11 and KEAP1 mutated NSCLC patients."

The abstract will be available on the Company’s website in the Scientific Presentations portion of the Investors section.

On April 18, 2023 Athersys, Inc. (the "Company") entered into a securities purchase agreement with each purchaser identified on the signature pages thereto (the "Purchase Agreement"), pursuant to which the Company agreed to issue and sell, in a public offering, (i) an aggregate of 2,315,000 shares (the "Shares") of the Company’s common stock, par value $0.001 per share (the "Common Stock") and (ii) pre-funded warrants (the "Pre-Funded Warrants") exercisable for an aggregate of 1,370,000 shares of Common Stock (the "Pre-Funded Warrant Shares"), together with warrants (the "Common Warrants" and, collectively with the Pre-Funded Warrants, the "Warrants") exercisable for an aggregate of 3,685,000 shares of Common Stock (collectively with the Pre-Funded Warrant Shares, the "Warrant Shares") in a private placement (the "Offering"), in combinations of one Share or one Pre-Funded Warrant and one Common Warrant for a combined purchase price of $1.00 (less $0.0001 for each Pre-Funded Warrant) (Filing, 8-K, Athersys, APR 18, 2023, View Source [SID1234630226]). Subject to certain ownership limitations, the Pre-Funded Warrants are exercisable upon issuance, and the Common Warrants are exercisable upon the six-month anniversary of issuance. Each Pre-Funded Warrant is exercisable for one share of Common Stock at a price per share of $0.0001 (as adjusted from time to time in accordance with the terms thereof) and does not expire. Each Common Warrant is exercisable into one share of Common Stock at a price per share of $0.96 (as adjusted from time to time in accordance with the terms thereof) for a seven-year period after the six-month anniversary of the date of issuance. The Offering is expected to close on or about April 19, 2023, subject to customary closing conditions.

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The Shares, the Pre-Funded Warrants and the Pre-Funded Warrant Shares were offered and sold pursuant to a base prospectus, dated April 13, 2023, and a prospectus supplement, dated April 19, 2023, in connection with a takedown from the Company’s shelf registration statement on Form S-3 (Registration No. 333-264724).

Placement Agency Agreement

On April 18, 2023, the Company entered into a placement agency agreement (the "Placement Agency Agreement") with A.G.P./Alliance Global Partners ("A.G.P."), pursuant to which A.G.P. agreed to serve as exclusive placement agent for the issuance and sale of the Shares and Warrants. The Company has agreed to pay A.G.P. an aggregate cash fee equal to 6.5% of the gross proceeds received by the Company from the sale of the securities in the Offering. Pursuant to the Placement Agency Agreement, the Company also agreed to reimburse A.G.P. $65,000 for fees and expenses of legal counsel and other out-of-pocket expenses. The Placement Agency Agreement has indemnity and other customary provisions for transactions of this nature. A copy of the Placement Agency Agreement is attached as Exhibit 99.1 to this Current Report on Form 8-K and is hereby incorporated by reference herein.

The foregoing description of the Purchase Agreement, the Warrants and the Placement Agency Agreement are not complete and are qualified in their entirety by references to the full text of the Form of Purchase Agreement, the Form of Pre-Funded Warrant, the Form of Common Warrant and the Placement Agency Agreement, which are filed as exhibits to this Current Report on Form 8-K and are incorporated by reference herein.
A copy of the opinion of Jones Day relating to the validity of the securities issued in the Offering is filed herewith as Exhibit 5.1.

On April 18, 2023 Ashvattha Therapeutics ("Ashvattha"), a clinical-stage company advancing a new class of nanomedicine therapeutics that transverse tissue barriers to selectively target activated cells in regions of inflammation, reported preclinical data showing its potent macrophage switching nanomedicine, D-4559, reduces tumor growth in a mouse model of hepatocellular carcinoma (HCC) (Press release, Ashvattha Therapeutics, APR 18, 2023, View Source [SID1234630225]). The data was presented in a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting taking place at the Orange County Convention Center in Orlando, Florida from April 14th through 19th.

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D-4559 is a new class of tyrosine kinase inhibitors referred to as Dendranibs, which specifically target activated macrophages and microglia in regions of inflammation. D-4559 is designed using the sorafenib backbone to selectively inhibit VEGFR tyrosine kinases in tumor associated macrophages (TAMs) leading to a functional reprogramming of TAMs toward a pro-inflammatory activated phenotype, allowing the immune system to better eliminate cancerous cells.

"We have combined the selectivity of our precision nanomedicine therapeutics with the ability to modulate the state of TAMs creating a unique approach to fighting cancer," said Jeff Cleland, CEO and chairman of Ashvattha Therapeutics. "We have observed with our other novel dendranib (D-4517.2) the ability to avoid the side effects of typical tyrosine kinase inhibitors. D-4559 offers an approach to safely creating a pro-inflammatory tumor microenvironment potentially improving anti-tumor immune response."

Key details and takeaways from the poster presentation include:

In vivo efficacy of D-4559 was examined in the subcutaneous Hepa 1-6 liver tumor mouse model and compared with sorafenib, a tyrosine kinase inhibitor used to treat kidney and liver cancers
D-4559 creates a pro-inflammatory tumor microenvironment which significantly reduced tumor growth when compared to vehicle-treated control group
D-4559-treated mice demonstrated a significantly greater M1:M2 TAM ratio compared to sorafenib-treated mice
D-4559 significantly increased plasma TNF-α and IL-8 cytokines, which has been correlated with better survival in patients with liver cancer

On April 18, 2023 Ariceum Therapeutics (Ariceum), a private biotech company developing radiopharmaceutical products for the diagnosis and treatment of certain hard-to-treat cancers, reported the successful completion of a Series A extension financing, raising a further EUR 22.75 million, following the EUR 25 million Series A financing announced in June 2022 (Press release, Ariceum Therapeutics, APR 18, 2023, View Source [SID1234630224]). The financing was co-led by new investors Andera Partners and Earlybird Venture Capital, with participation from existing investor Pureos Bioventures, now doubling its original investment in the Company. As part of the investment, Olivier Litzka, Partner at Andera Partners, and Christoph Massner, Principal at Earlybird, will join the Ariceum Board of Directors.

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Ariceum intends to use the proceeds from the financing to advance its clinical pipeline and to further build the Company focusing on its lead asset and proprietary peptide derivative, Satoreotide, as well as building a pipeline of further projects.

Satoreotide is a radiopharmaceutical drug and an antagonist of the somatostatin type 2 (SST2) receptor which is overexpressed in many cancers, including certain neuroendocrine and other aggressive, hard-to-treat cancers with poor prognoses such as small cell lung cancer (SCLC). Ariceum aims to use satoreotide as a ‘theranostic’ for both the diagnosis and treatment of tumours expressing the SST2 receptor. Satoreotide is in early clinical development and, as of today, has been administered to more than 100 patients including more than 150 therapeutic administrations in different indications.

Manfred Rüdiger, PhD, Chief Executive Officer of Ariceum Therapeutics, said: "As we continue to make promising progress at Ariceum, the new funds will allow us to advance our clinical pipeline of diagnosis, monitoring and precision treatments to improve the lives of those facing very challenging cancers. The additional investment is a strong endorsement of our targeted radiotherapy product and reflects the opportunity that radiopharmaceutical drugs offer in visualizing and treating cancer. We are very pleased to welcome both Andera Partners and Earlybird Venture Capital to our investment syndicate and would like to thank our existing investors for their continued support."

Olivier Litzka, PhD, Partner of Andera Partners, remarked: "At Andera we have been following the radiopharmaceuticals space for some time, looking for an opportunity to support a compelling project. As a result, we are now very happy to be able to back the talented and experienced team of Ariceum with a first clinical project centered around a meaningful disease application in Small Cell Lung Cancer. It is great to support the company in its bold ambition to build a pipeline of radiopharma projects through deals and partnerships. We are also joining an already powerful board of experts and strong European VCs. Altogether, we believe these are solid grounds to build a leading biotech company in the radiopharmaceuticals field."

Christoph Massner, PhD, Principal of Earlybird Venture Capital, commented: "We are delighted to support Ariceum as it advances its proprietary clinical programs to address aggressive cancers with a poor prognosis. Earlybird is especially excited about Ariceum’s ability to stratify patients for treatment via its theranostics approach. This will provide the best possible patient outcomes and attractive health economics. I look forward to working with Ariceum’s experienced management team and strong investor base as it enters its next development stage.