On August 9, 2024 Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb reported the submission of supplemental application of Ono’s anti-PD-1 antibody, Opdivo (generic name: nivolumab) Intravenous Infusion ("Opdivo") and BMSKK’s anti-CTLA-4 antibody, Yervoy (generic name: ipilimumab) Injection ("Yervoy") in combination therapy in Japan, to expand the use for the treatment of unresectable hepatocellular carcinoma (HCC) (Press release, Ono, AUG 9, 2024, View Source [SID1234646251]). This application is related to the additional indication for a partial change in approved items of the manufacturing and marketing approval in Japan.

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 This application is based on the results from interim analysis of the CheckMate -9DW study, a global multi-center Phase 3 clinical study (CA209-9DW: ONO-4538-92), evaluating Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib monotherapy for patients with unresectable HCC who have not received prior systemic therapy. In this study, Opdivo plus Yervoy met its primary endpoint of overall survival (OS), demonstrating a statistically significant and clinically meaningful improvement in OS compared to lenvatinib or sorafenib monotherapy. The safety profile of Opdivo plus Yervoy was consistent with previously reported data, with no new safety signals identified.

About CheckMate -9DW Study (CA209-9DW: ONO-4538-92)
 CheckMate -9DW study is a global multicenter randomized open-label Phase 3 study evaluating the combination of Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib monotherapy in patients with advanced hepatocellular carcinoma who have not received prior systemic therapy.
 668 patients were randomized to receive Opdivo plus Yervoy (Opdivo 1 mg/kg plus Yervoy 3 mg/kg Q3W for up to four doses, followed by Opdivo monotherapy 480 mg Q4W) infusion, or single agent lenvatinib or sorafenib as oral capsules in the control arm. The primary endpoint of the study is overall survival (OS) and key secondary endpoints include objective response rate (ORR) and time to symptom deterioration (TTSD).

About Hepatocellular Carcinoma
 Liver cancer is the third most frequent cause of cancer death worldwide. It is estimated that there were approximately 866,000 new cases of liver cancer worldwide in 2022, with an estimated approximately 758,000 deaths1) . In Japan, it is estimated that there were approximately 41,000 new cases of liver cancer in 2022, with an estimated approximately 26,000 deaths1) . Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for 90% of all liver cancers2) . HCC is often diagnosed in an advanced stage, where effective treatment options are limited and are usually associated with poor outcomes.
 Up to 70% of patients experience recurrence within five years, particularly those still considered to be at high risk after surgery or ablation3) . While most cases of HCC are caused by hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, metabolic syndrome and nonalcoholic steatohepatitis (NASH) are rising in prevalence and expected to contribute to increased rates of HCC.

Globocan 2022: Available at: View Source
Kim E, Viatour P. Hepatocellular carcinoma: old friends and new tricks. Exp Mol Med. 2020; 52: 1898–07.
Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018; 391: 1301–14.
About Opdivo
 Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response by blocking the interaction between PD-1 and its ligands. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers since the approval for the treatment of melanoma in Japan in July 2014. Opdivo is currently approved in more than 65 countries, including Japan, South Korea, Taiwan, the US and European Union.
 In Japan, Ono launched Opdivo for the treatment of unresectable melanoma in September 2014. Thereafter, Opdivo received an approval for additional indications of unresectable advanced or recurrent non-small cell lung cancer in December 2015, unresectable or metastatic renal cell carcinoma in August 2016, relapsed or refractory classical Hodgkin lymphoma in December 2016, recurrent or metastatic head and neck cancer in March 2017, unresectable advanced or recurrent gastric cancer which has progressed after chemotherapy in September 2017, unresectable advanced or recurrent malignant pleural mesothelioma which has progressed after chemotherapy in August 2018, microsatellite instability high (MSI-High) unresectable advanced or recurrent colorectal cancer that has progressed following chemotherapy and unresectable advanced or recurrent esophageal cancer that has progressed following chemotherapy in February 2020, cancer of unknown primary in December 2021, adjuvant treatment of urothelial carcinoma in March 2022, malignant mesothelioma (excluding malignant pleural mesothelioma) in November 2023 and unresectable advanced or recurrent malignant epithelial tumors in February 2024.
 In addition, Ono has been conducting clinical development program including hepatocellular carcinoma, etc.

About Yervoy
 Yervoy is a recombinant, human monoclonal antibody, and binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation. Yervoy binds to CTLA-4, and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is now approved in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types. In Japan, Yervoy was approved for the indication of unresectable malignant melanoma in July 2015.

About Ono and Bristol Myers Squibb Collaboration
 In 2011, through a collaboration agreement with Bristol Myers Squibb (BMS), Ono granted BMS its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to Opdivo except the US at the time. In July 2014, Ono and BMS further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agent and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

On August 9, 2024 Invenio Imaging, a leader in intraoperative fresh tissue imaging and artificial intelligence (AI), reported the enrollment of the first patients in a US pivotal study of its AI-based image analysis module for lung cancer (Press release, Invenio, AUG 9, 2024, View Source [SID1234645695]). The ON-SITE study, a multicenter study in bronchoscopy combining Stimulated Raman Histology with Artificial Intelligence for rapid lung cancer detection, is in collaboration with Johnson & Johnson Enterprise Innovation Inc. and will be conducted at multiple centers including The University of Texas MD Anderson Cancer Center, Corewell Health, Memorial Sloan Kettering Cancer Center, and University of North Carolina at Chapel Hill.

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Lung cancer is the leading cause of cancer-related deaths in the United States. This has led to the institution of large-scale screening programs for high-risk patients, which results in an estimated 3.1 million new primary lung nodules identified each year. Despite major sector investment in minimally-invasive biopsy technology, obtaining adequate tissue for biomarker and treatment determination remains a challenge. For this reason, bronchoscopy guidelines recommend rapid-on-site tissue evaluation (ROSE) for lung biopsies.

"ROSE requires that a cytologist or highly trained cytotechnician be physically present in the procedure room, and thus it is not available at many centers performing lung biopsy due to resource limitations," said Jason Akulian, MD, Director of Interventional Pulmonlogy at UNC, "we are excited by the NIO’s potential to extend the benefits of ROSE to the proceduralist when the service is not available."

The NIO Laser Imaging System allows rapid imaging of fresh tissue biopsies in the treatment room. Sample preparation does not require staining or sectioning and can be performed by the existing OR-staff. NIO Slides are also designed to allow retrieval of the sample for downstream analysis. NIO images are natively digital and can be shared in near real-time. The ON-SITE study aims to develop and validate an AI-based image analysis module for the NIO Laser Imaging System that is intended to assist physicians in the detection of cancer in bronchoscopic lung biopsies in situations where ROSE is not available for the sample type.

"Artificial intelligence aiding healthcare may seem utopic, but the future is coming. While still investigational, the promise of fast, in-room, accurate identification of tissue that is suspicious for cancer has the potential to ultimately lead to improved outcomes, a beneficial cost/benefit profile, and personalized treatments," said Gustavo Cumbo-Nacheli, MD, pulmonologist at Corewell Health and one of the site PIs for the ON-SITE study.

"Enrolling the first patient in the ON-SITE study is an important milestone for Invenio, as we aim to develop the first FDA-cleared AI to identify cell/tissue morphology suspicious for cancer in lung biopsies," said Jay Trautman, PhD, co-founder and CEO of Invenio Imaging. "Near real-time image analysis on the NIO Laser Imaging System completes the end-to-end solution for streamlined intraoperative histology."

On August 9, 2024 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, reported financial results for the quarter ended June 30, 2024, and highlighted recent corporate accomplishments (Press release, Zentalis Pharmaceuticals, AUG 9, 2024, View Source [SID1234645694]).

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"While we faced challenges this quarter with regards to the ongoing partial clinical hold on azenosertib, we remain steadfast in our confidence in the program’s therapeutic potential and in our commitment to bringing this investigational medicine to patients with gynecological malignancies," said Kimberly Blackwell, M.D., Chief Executive Officer. "We continue to engage with regulators to resolve the hold and advance our clinical development efforts, which have already made important progress this year. Notably, we announced this quarter that we look forward to sharing the results of Cohort 1b of our DENALI study, a study that enrolled heavily pretreated platinum resistant ovarian cancer patients. We are grateful to our study investigators who continue to believe in the potential of azenosertib, to our employees who are laser-focused on our goal of making azenosertib available to patients, and most importantly, our clinical study participants and their families for their support."

Program Updates
•Azenosertib development update. On June 18, 2024, Zentalis disclosed that the U.S. Food and Drug Administration (FDA) placed a partial clinical hold on certain clinical studies of azenosertib. The action followed two recent deaths in the DENALI study. Zentalis will provide additional updates to the azenosertib clinical development and certain data timelines following resolution of the partial clinical hold.
•Phase 1 azenosertib clinical data in osteosarcoma presented at ASCO (Free ASCO Whitepaper). In accordance with the Company’s guidance, Phase 1 results of azenosertib in combination with gemcitabine in adult and pediatric patients with relapsed or refractory (R/R) osteosarcoma were presented in a poster session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
•Acute myeloid leukemia (AML) program update. Today, Zentalis is disclosing that it is no longer developing the combination of its BCL-2 inhibitor, ZN-d5, with azenosertib, and is discontinuing development of ZN-d5. The combination of ZN-d5 and azenosertib was studied in 27 patients with R/R AML in a Phase 1 study. Thirteen patients were evaluable for efficacy, and the other 14 patients experienced progressive disease prior to efficacy evaluation or withdrew. The combination demonstrated clinical activity in patients who had been previously treated with venetoclax. Of the 6 patients who completed at least two cycles of therapy and underwent a cycle 3, day 1 bone marrow (BM) aspirate: 1 achieved a complete remission with incomplete hematologic recovery (CRi) and became transplant eligible, 2 patients had decreased BM blast counts, 2 had stable BM blasts, and 1 patient had increased BM blasts. The safety profile was manageable and in-line with other combinations in the R/R AML disease setting.

Corporate Updates
•Today, Zentalis is disclosing that effective August 8, 2024, Diana Hausman, M.D., has stepped down and is no longer serving as the Company’s Chief Medical Officer. The Company is conducting a search for a new Chief Medical Officer. Dr. Blackwell will serve as the Company’s Interim Chief Medical Officer.
•On May 29, 2024, Zentalis announced the appointment of Luke Walker, M.D., to its Board of Directors. Dr. Walker is the Chief Medical Officer of Harpoon Therapeutics, a subsidiary of Merck & Co., Inc., Rahway, NJ, and brings nearly three decades of experience as a practicing oncologist and drug developer advancing new cancer therapies.

Anticipated Upcoming Milestones
•2H 2024
◦Topline results from Cohort 1b of the Phase 2 DENALI study (ZN-c3-005) of azenosertib monotherapy in platinum resistant high-grade serous ovarian cancer
◦Presentation of final results of Phase 1b (ZN-c3-001) azenosertib monotherapy trial in solid tumors
◦Topline data from Phase 1/2 MAMMOTH (ZN-c3-006) azenosertib + PARP inhibitor (niraparib) and azenosertib monotherapy trial in platinum resistant ovarian cancer in partnership with GSK
◦Presentation of initial data from Phase 1 (ZN-c3-016) azenosertib + BEACON regimen (encorafenib + cetuximab) trial in BRAF mutant metastatic colorectal cancer in partnership with Pfizer
◦Additional updates to the azenosertib clinical development and other data timelines to be provided following resolution of the partial clinical hold.

Second Quarter 2024 Financial Results
•Cash, Cash Equivalents and Marketable Securities Position: As of June 30, 2024, Zentalis had cash, cash equivalents and marketable securities of $426.4 million, which includes $27.8 million representing the June 30, 2024 fair value of Immunome common stock received by the Company as part of its upfront payment for the out-licensing of its ROR1 antibody-drug conjugate (ADC) product candidate and ADC platform in January 2024. The Company believes that its existing cash, cash equivalents and marketable securities (excluding the Immunome stock) as of June 30, 2024 will be sufficient to fund its operating expenses and capital expenditure requirements into mid-2026.

•Research and Development Expenses: Research and development (R&D) expenses for the three months ended June 30, 2024, were $48.4 million, compared to $42.7 million for the three months ended June 30, 2023. The increase of $5.7 million was primarily due to increases of $7.4 million for clinical and certain translational expenses and $1.0 million for drug manufacturing and supplies costs. The Company also saw increases of $1.4 million resulting from no R&D cost sharing arrangement with Zentera. These increases were partially offset by a decrease of $2.7 million of personnel expense of which $1.5 million is related to non-cash stock-based compensation and $1.4 million of facilities and allocated expenses.

•General and Administrative Expenses: General and administrative expenses for the three months ended June 30, 2024, were $16.8 million, compared to $15.7 million during the three months ended June 30, 2023. This increase of $1.1 million was primarily attributable to an increase in personnel expenses of $1.3 million and lease termination costs of $0.5 million. This was partially offset by a decrease of other expenses of $0.7 million, net.

About Azenosertib

Azenosertib is a novel, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated as a monotherapy and combination clinical studies in ovarian cancer and additional tumor types. WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints, through negative regulation of both CDK1 and CDK2, to prevent replication of cells with damaged DNA. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage and leading to mitotic catastrophe and cancer cell death.

On August 9, 2024 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported its recent accomplishments and financial results for the quarter ended June 30, 2024 (Press release, Soligenix, AUG 9, 2024, View Source [SID1234645693]).

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"This is a pivotal time for Soligenix with a great deal of clinical activity and upcoming milestones," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "While we prepare for the upcoming initiation of our confirmatory Phase 3 placebo-controlled study evaluating the safety and efficacy of HyBryte (synthetic hypericin) in the treatment of cutaneous T-cell lymphoma (CTCL) patients with early-stage disease, we are incredibly encouraged by the recent positive clinical results from our comparability study evaluating HyBryte against Valchlor (mechlorethamine gel), which demonstrated a three-fold higher response rate over a 12-week treatment period and more favorable safety profile for HyBryte in the treatment of CTCL. These findings, coupled with the promising interim data from the ongoing open-label, investigator-initiated study evaluating extended HyBryte treatment, reinforce our excitement about the future of HyBryte as a potential front-line treatment option for patients with early-stage CTCL. Additionally, we will be initiating a Phase 2 study with SGX945 (dusquetide) in Behçet’s disease later this year with top-line results expected in the first half of 2025, along with top-line results expected during the same timeframe from our ongoing SGX302 (synthetic hypericin) Phase 2 study in mild-to-moderate psoriasis."

Dr. Schaber continued, "With approximately $9.1 million in cash at June 30, 2024, exclusive of the approximately $4.1 million in net proceeds from recent warrant exercises, we continue to prioritize resource allocation to achieve our goals. We have a clear vision for the future, and we are actively pursuing strategies to create long-term value for our shareholders, including but not limited to, partnership and merger and acquisition opportunities."

Soligenix Recent Accomplishments

On July 24, 2024, the Company received a letter from Nasdaq confirming that the Company had regained compliance with the Minimum Bid Price Rule. Accordingly, the Nasdaq Hearings Panel determined to continue the listing of the Company’s common stock and closed the matter.
On July 9, 2024, the Company announced an interim update on the open-label, investigator-initiated study evaluating extended HyBryte treatment for up to 12 months in patients with early-stage CTCL. To view this press release, please click here.
On June 25, 2024, the Company announced positive clinical results from a comparability study evaluating HyBryte versus Valchlor in the treatment of CTCL. To view this press release, please click here.
On May 16, 2024, the Company announced the publication of results of its compatibility study evaluating HyBryte for the treatment of CTCL in the Journal of the European Academy of Dermatology & Venereology (JEADV) Clinical Practice. To view the publication, please click here. To view this press release, please click here.
Financial Results – Quarter Ended June 30, 2024

Soligenix’s revenues for the quarter ended June 30, 2024 were less than $0.1 million as compared to $0.2 million for the quarter ended June 30, 2023. Revenues primarily relate to government contracts and grants awarded in support of SGX943 for treatment of emerging and/or antibiotic-resistant infectious diseases; development of CiVax, our vaccine candidate for the prevention of COVID-19, and evaluation of HyBryte for expanded treatment in patients with early-stage CTCL.

Soligenix’s net loss was $1.6 million, or ($1.31) per share, for the quarter ended June 30, 2024, as compared to $1.6 million, or ($3.56) per share, for the quarter ended June 30, 2023. The increase in net loss was primarily due to decreases in gross profit and tax credits as well as an increase in operating expenses, offset by increases in interest income and changes in the fair value of debt during the three months ended June 30, 2024.

Research and development expenses were $0.5 million as compared to $0.8 million for the quarters ended June 30, 2024 and 2023, respectively. The decrease was primarily due to adjustment of estimated accruals for completed clinical trials offset by preliminary costs associated with the anticipated initiation of our Phase 2 study in Behçet’s Disease and the second Phase 3 CTCL trial.

General and administrative expenses were $1.2 million and $0.9 million for the quarters ended June 30, 2024 and 2023, respectively. The increase in general and administrative expenses for the three months ended June 30, 2024 was primarily attributable to an increase in legal and professional fees associated with the 2024 annual meeting of stockholders, the April 2024 public offering and the June 2024 reverse stock split of our issued and outstanding shares of common stock.

As of June 30, 2024, the Company’s cash position, exclusive of the approximately $4.1 million in net proceeds from recent warrant exercises, was approximately $9.1 million.

On August 9, 2024 Scorpius Holdings, Inc. (NYSE American: SCPX), ("Scorpius", or the "Company"), an integrated contract development and manufacturing organization (CDMO), reported a delay in its previously announced public offering (Press release, Scorpius BioManufacturing, AUG 9, 2024, View Source [SID1234645687]). The Company has requested, and the NYSE has approved, a financial viability exception to the NYSE American shareholder approval rules that would allow it to proceed with the closing of an underwritten public offering. The Company intends to pursue the sale of 12,500,000 shares of common stock (or pre-funded warrants ("Pre-Funded Warrants") in lieu thereof, exclusive of the over-allotment option) at a price of $1.00 per share (inclusive of the Pre-Funded Warrant exercise price). The underwriting agreement was terminated in connection with the previously announced offering and a new underwriting agreement will be entered into if the offering is consummated. There can be no assurance that the Company will be able to consummate an offering under these terms or otherwise. The Company will adhere to all applicable provisions relating to the exemption, as outlined in Section 710 of the NYSE American Company Guide, and a closing is intended to occur ten days following the mailing of a notification letter to the Company’s shareholders.

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The Company intends to use the net proceeds of the offering to fund working capital and for general corporate purposes.

ThinkEquity is acting as sole book-running manager for the offering.

A registration statement on Form S-1 (File No. 333-280887), as amended, including a preliminary prospectus, relating to the securities being offered was filed with the Securities and Exchange Commission ("SEC") and became effective on August 6, 2024. This offering is being made only by means of a prospectus. Copies of the final prospectus, when available, may be obtained from ThinkEquity, 17 State Street, 41st Floor, New York, New York 10004. The final prospectus will be filed with the SEC and will be available on the SEC’s website located at View Source

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.