On February 21, 2023 PDX Pharma reported that it has been awarded a phase II SBIR grant of $1.87M for 2 years from the National Cancer Institute (NCI) focusing on the development of a new nano-immunotherapy ARAC-02 (Antigen Release Agent and Checkpoint Inhibitor) for lung cancer treatment (Press release, PDX Pharmaceuticals, FEB 21, 2023, View Source [SID1234627466]). ARAC-02 – nanoparticle co-delivering a PD-L1 antibody, a polo-like kinase 1 (PLK1) inhibitor, and an immune-stimulant CpG – provides effective antitumor immune response via CD8+ T cell activities. The original grant application of ARAC-02 had high merit and received a rare perfect score from the NIH. We met all phase I SBIR milestones on formulation optimization and initial efficacy and safety studies in cells and in mice, which leads to phase II SBIR grant awarded for ARAC-02’s evaluation in multiple lung cancer models. Many cancers including lung cancer depend on PLK1 for cell division and growth, and PLK1 inhibition by ARAC-02 will lead to cell death. After PLK1 inhibition, ARAC-02 transiently upregulates PD-L1 expression, rendering the cancer (which may originally have low PD-L1 expression and are not eligible for immune checkpoint inhibitors, ICIs) more sensitive to PD-L1 antibody serving as the ICI and cancer homing agent on ARAC-02. We also show that CpG on ARAC-02, which recruits and activates antigen-presenting cells, enhance CD8+ T cell population and activities. Our current data suggest that ARAC-02 will have broad efficacy in lung and other cancer types (e.g., breast, liver, and pancreatic cancer) regardless of mutational status. ARAC-02 is anticipated to reach clinical trials next year. Data on first gen ARAC (without CpG) was published in Nature Communications in 2022. A US patent (US11224573B2) on the ARAC technology was also issued in Jan, 2022.

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On February 21, 2023 iBio CDMO LLC, a wholly owned subsidiary of iBio, Inc. (the "Company") and Woodforest National Bank ("Woodforest") reported that it has entered into the Second Amendment to the Credit Agreement that was entered into on November 1, 2021, as amended (the "Credit Agreement"), which amendment, among other things, added a milestone that had to be met by a specified date, the failure of which would be an event of default (Filing, 8-K, iBioPharma, FEB 21, 2023, View Source [SID1234627464]). In addition, on February 9, 2023, the Company, as guarantor, entered into the Second Amendment to the Guaranty, which was executed on November 1, 2021, as amended (the "Guaranty"), which amendment, among other things, allows the Company to account for all amounts owed to it by Fraunhofer USA Inc. ("Fraunhofer") as part of its legal settlement with them (the "Fraunhofer Settlement Funds") in determining whether the Company is in compliance with the Liquidity Covenant (as defined in the Credit Agreement, which currently is a requirement that the Company maintain $7,500,000 in unrestricted cash) until a specified period dependent upon the occurrence of a specific milestone in the Credit Agreement.

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On February 20, 2023, iBio CDMO LLC entered into the Third Amendment to the Credit Agreement, which removed the added milestone specified in the Second Amendment, the failure of which would be an event of default. In addition, the Guaranty was amended to allow the Company until February 28, 2023, to account for the Fraunhofer Settlement Funds in determining whether the Company is in compliance with the Liquidity Covenant without being dependent upon a specified milestone. In addition, the Company agreed that each time it consummates an at-the-market issuance of Equity Interests (as defined within the Credit Agreement), no later than five (5) days following such issuance of Equity Interests, it will (a) pay to Woodforest in immediately available cash funds, without setoff or counterclaim of any kind, forty percent (40%) of the Net Proceeds (as defined within the Credit Agreement) received by the Company for such issuance of Equity Interests; provided, any such payment would cease upon payment obligations in full and (b) provide Woodforest with a detailed accounting of each such issuance of Equity Interests.

As a result of the payment of $2,1000,00 we received related to the Auction Sale Agreement we entered into on February 10, 2023, with Holland Industrial Group, together with Federal Equipment Company and Capital Recovery Group, LLC, we are currently in compliance with the Liquidity Covenant without including the Fraunhofer Settlement Funds in such calculation. However, based on current estimates, without additional funds, we do not anticipate being in compliance with the covenant on February 28, 2023 if we are unable to include the Fraunhofer Settlement Funds in such calculation. If the Company is unable to increase its unrestricted cash by February 28, 2023, and fails to meet the Liquidity Covenant, it would be in default of the terms of the Credit Agreement and the Guaranty and another amendment to the Credit Agreement and Guaranty may be necessary. The Company and Woodforest continue to be in discussions regarding a potential default and potential amendment to the Credit Agreement to rectify any such default.

The descriptions of the Third Amendment to the Credit Agreement and the Third Amendment to the Guaranty do not purport to be complete and are qualified in their entirety by reference to the Third Amendment to the Credit Agreement and the Third Amendment to the Guaranty, copies of which are filed as Exhibit 10.1 to this Current Report on Form 8-K and is incorporated herein by reference.

On February 21, 2023 Halozyme Therapeutics, Inc. (NASDAQ: HALO) ("Halozyme") reported its financial and operating results for the fourth quarter and full year ended December 31, 2022 and provided an update on its recent corporate activities and outlook (Press release, Halozyme, FEB 21, 2023, View Source [SID1234627463]).

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"Our strong performance across the business, including the successful integration of Antares Pharma, drove another year of record revenue of $660 million, representing 49% year-over-year growth," said Dr. Helen Torley, president and chief executive officer of Halozyme. "In 2023, we continue to project record revenue of $815 to $845 million and greater than 30% growth in EBITDA to $415 to $440 million, driven by diversified revenue streams. I am excited with the opportunity for two partner regulatory approvals in 2023 for products utilizing ENHANZE, SC efgartigimod for generalized myasthenia gravis and SC atezolizumab. With the addition of Antares to the Halozyme portfolio, we are enthusiastic about our ability to expand our partnerships with ENHANZE and the auto-injector technology."

Recent Partner Highlights:
•Bristol Myers Squibb plans to initiate a Phase 3 trial in early 2023 to demonstrate the drug exposure level of nivolumab plus relatlimab fixed-dose combination with ENHANZE is not inferior to intravenous administration in participants with previously untreated metastatic or unresectable melanoma. This is in addition to two ongoing Phase 3 studies comparing nivolumab administrated intravenously to nivolumab administered subcutaneously in patients with renal cell carcinoma and melanoma.
•In December 2022, Takeda achieved a sales milestone for HYQVIA, triggering a payment of $10 million.
•In November 2022, Roche submitted a Biologics License Application to the FDA and a Marketing Authorization Application to the European Medical Agency (EMA) for SC atezolizumab with ENHANZE across all approved indications of IV Tecentriq. In January

2023, Roche announced the FDA accepted the Biologics License Application with a PDUFA date of September 15, 2023.
•In November 2022, Roche submitted an Initial Market Application for Mabthera subcutaneous (SC) to the Center for Drug Evaluation in China.
•In November 2022, argenx announced the acceptance of the Biologics License Application for SC efgartigimod for the treatment of adults with generalized myasthenia gravis. In January 2023, argenx announced that the FDA extended the PDUFA date to June 20, 2023.
•In November 2022, argenx announced the submission of a Marketing Authorization Application to the EMA for SC efgartigimod for the treatment of adults with generalized myasthenia gravis.
•In October 2022, Roche Pharmaceuticals China announced the approval of Herceptin SC (trastuzumab injection subcutaneous with ENHANZE) in China for the treatment of patients with early-stage and metastatic HER2-positive breast cancer.
•In July 2022, Takeda announced positive topline results from the pivotal phase 3 ADVANCE clinical trial evaluating HYQVIA for the maintenance treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and the company confirmed its intention to submit regulatory applications in the United States and European Union in its fiscal year 2022.

Recent Corporate Highlights:
•In February 2023, Halozyme elected Barbara Duncan to its Board of Directors.
•In January 2023, Halozyme elected to redeem on March 17, 2023 all if its outstanding 1.25% convertible senior notes due 2024.
•In December 2022, Halozyme completed an Accelerated Share Repurchase agreement to repurchase $110 million of common stock. Halozyme received a total of 2.4 million shares at an average price per share of $45.62. During 2022, the Company repurchased a total of 4.5 million shares for $200 million at an average price per share of $44.44, and as of December 31, 2022, Halozyme has completed $350 million of its 3-year, $750 million dollar share repurchase plan, at an average price per share of $41.69.

Fourth Quarter and Full Year 2022 Financial Highlights:
•Revenue for the fourth quarter was $181 million compared to $102.0 million for the fourth quarter of 2021. The 78% year-over-year increase was driven by an increase in royalty revenue primarily attributable to subcutaneous DARZALEX (daratumumab) and the addition of product sales as a result of the Antares Pharma acquisition. Revenue for the quarter included $106.0 million in royalties, an increase of 69% compared to $62.6 million in the prior year period.
Total revenue for the full year was $660.1 million, compared with $443.3 million in 2021, representing 49% year-over-year growth.
•Cost of sales for the fourth quarter was $42.1 million, compared to $21.6 million for the fourth quarter of 2021. The increase was driven by an increase in product sales as a result of the Antares Pharma acquisition.
Cost of sales for the full year was $139.3 million, compared to $81.4 million in 2021, primarily driven by an increase in sales in our proprietary and partnered products as a result of the Antares Pharma acquisition and amortization of inventory step-up associated with purchase accounting for the acquisition.
•Amortization of intangibles expense in the fourth quarter and full year was $4.6 million and $43.1 million, respectively, an increase from no expense in the fourth quarter and full year of 2021, due to the Antares Pharma acquisition, in which Halozyme acquired intangible assets that are amortized over a useful life related to the auto injector technology platform, XYOSTED and TLANDO.

•Research and development expenses for the fourth quarter and full year were $22.6 million and $66.6 million, respectively, compared to $10.1 million and $35.7 million for the fourth quarter and full year of 2021, respectively. Selling, general and administrative expenses for the fourth quarter and full year were $37.7 million and $143.5 million, respectively, compared to $13.8 million and $50.3 million for the fourth quarter and full year of 2021 respectively. The increases were primarily due to planned investments in ENHANZE, the Antares Pharma acquisition and increases in compensation expense related to the combined workforce.
•Operating income in the fourth quarter was $74.5 million, compared to operating income of $56.5 million in the fourth quarter of 2021. Operating income for the full year was $267.5 million, compared to $275.9 million in 2021.
•Net Income on a GAAP basis in the fourth quarter of 2022 was $57.7 million, compared with net income of $66.8 million in the fourth quarter of 2021 and for the full year was $202.1 million, compared to net income of $402.7 million in 2021, which includes the reversal of the valuation allowance recorded against the Company’s deferred tax assets and resulted in the recognition of a one-time non-cash income tax benefit during the prior year quarter and full year of $12 million and $154.2 million, respectively.
•Earnings per Share: On a GAAP basis in the fourth quarter of 2022, diluted earnings per share was $0.42, compared with $0.46 in the fourth quarter of 2021. On a non-GAAP basis diluted earnings per share was $0.48, compared with diluted earnings per share of $0.42 in the fourth quarter of 2021.1
GAAP diluted earnings per share for the full year was $1.44 compared with $2.74 per share in 2021. The 2021 GAAP results include a one-time recognition of a non-cash income tax benefit of $1.05 per share. Non-GAAP diluted earnings per share for the full year was $2.21 per share, compared to $2.00 per share in 2021.
•Cash, cash equivalents and marketable securities were $362.8 million on December 31, 2022, compared to $740.9 million on December 31, 2021.

Financial Outlook for 2023

The Company is reiterating its financial guidance for 2023, which was initially provided on January 10, 2023. For the full year 2023, the Company expects:

•Total revenue of $815 million to $845 million, representing growth of 23% to 28% over 2022 total revenue primarily driven by continued strength in Wave 2 products, including DARZALEX SC (daratumumab) and Phesgo (pertuzumab, trastuzumab and hyaluronidase) utilizing ENHANZE technology, as well as full year auto-injector royalty and product contribution. The Company expects revenue from royalties of $445 million to $455 million, representing growth of 23% to 26%.
•EBITDA of $415 million to $440 million, representing growth of >30% over 2022. EBITDA excludes the impact of amortization costs related to the Antares Pharma acquisition.1
•Non-GAAP diluted earnings per share of $2.50 to $2.65, representing growth of >10% over 20221. The Company’s earnings per share guidance does not consider the impact of potential future share repurchases.

Table 1. 2023 Financial Guidance

Guidance Range
Total Revenue $815 to $845 million
Royalty Revenue $445 to $455 million
EBITDA $415 to $440 million
Non-GAAP Diluted EPS $2.50 to $2.65

Webcast and Conference Call

Halozyme will host its Quarterly Update Conference Call for the fourth quarter ended December 31, 2022 today, Tuesday, February 21, 2023 at 4:30 p.m. ET/1:30 p.m. PT. The conference call may be accessed live with pre-registration via this link: View Source The call will also be webcast live through the "Investors" section of Halozyme’s corporate website and a recording will be made available following the close of the call. To access the webcast and additional documents related to the call, please visit the "Investors" section of www.halozyme.com.

On February 21, 2023 BioXcel Therapeutics presenting its corporate presentation (Presentation, BioXcel Therapeutics, FEB 21, 2023, View Source [SID1234627460]).

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On February 21, 2023 Aileron Therapeutics (Nasdaq: ALRN) reported that a review of initial data from its Phase 1b chemoprotection trial of ALRN-6924 in patients with p53-mutated breast cancer showed that patients in the trial experienced severe neutropenia (Grade 4) and alopecia (Press release, Aileron Therapeutics, FEB 21, 2023, View Source [SID1234627459]). The primary endpoint of the Phase 1b open-label trial, which was evaluating ALRN-6924 in patients with breast cancer receiving neoadjuvant or adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide, or "TAC" chemotherapy, was duration and incidence of severe neutropenia in cycle 1. Incidence of chemotherapy-induced alopecia (hair loss) was a secondary endpoint. Based on these findings, Aileron has decided to terminate the Phase 1b breast cancer trial and further development of ALRN-6924.

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Aileron also announced that it is exploring a range of strategic alternatives to maximize shareholder value. The company has engaged Ladenburg Thalmann & Co., Inc. to act as a strategic advisor for this process. Strategic alternatives that are being evaluated may include, but are not limited to, an acquisition, a merger, a business combination, a sale of assets or other transactions. There is no set timetable for this process and there can be no assurance that this process will result in Aileron pursuing a transaction or that any transaction, if pursued, will be completed on attractive terms. Aileron does not intend to comment further on this process unless or until its Board of Directors has approved a definitive course of action or it is determined that other disclosure is appropriate.

Aileron has determined to reduce its remaining workforce from 9 to 3 full-time employees in the coming weeks. The company plans to retain the remaining employees to assist in executing the strategic alternatives review process.

"We are very disappointed by these initial findings from our breast cancer trial, given the significant unmet need of cancer patients who must endure a wide range of chemotherapy-induced side effects and given the activity we had observed in our clinical trial in small cell lung cancer patients receiving topotecan chemotherapy. I would like to extend a heartfelt thanks to our patients, investigators and clinical trial staff and scientific advisors, as well as all others who have supported this trial and our efforts to advance ALRN-6924 as a chemoprotective agent. I would also like to thank our talented and truly dedicated Aileron team who have worked so diligently to advance ALRN-6924," said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron Therapeutics. "We certainly hoped for a much different outcome for patients, but it is imperative that we now shift our focus toward conserving our resources as we explore strategic alternatives to maximize shareholder value."

About ALRN-6924

ALRN-6924 is an MDM2/MDMX inhibitor that leverages Aileron’s proprietary peptide drug technology. Aileron originally initiated development of ALRN-6924 as an anti-cancer agent to restore p53-dependent tumor suppression in p53 wild-type tumors, evaluating ALRN-6924 as an anti-cancer agent in 196 patients in multiple clinical trials, including a single-agent Phase 1 trial in solid tumor and lymphoma patients [1]; a single-agent Phase 2a trial for the treatment of peripheral T-cell lymphoma (PTCL) [2]; a single-agent and Ara-C-combination Phase 1/1b trial for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) [3]; and a Phase 2a combination trial of ALRN-6924 and palbociclib in patients with tumors harboring MDM2 amplifications [4]. In these trials, ALRN-6924 was generally well-tolerated, with evidence of single-agent anti-tumor activity including complete and partial responses. Aileron has also conducted three clinical trials of ALRN-6924 as a chemoprotective agent in p53-mutated small cell lung cancer [5], non-small cell lung cancer, and breast cancer.

Aileron has a strong intellectual property portfolio in the U.S. and internationally and maintains exclusive worldwide rights to ALRN-6924 as well as the company’s proprietary peptide drug technology.

The company is based in Boston, Mass. Visit aileronrx.com to learn more.