On March 18, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported a clinical program comprising of trials studying Actimab-A in combination with either KEYTRUDA (pembrolizumab) or OPDIVO (nivolumab) which are blockbuster immunotherapies known as PD-1 inhibitors which are approved in multiple solid tumor indications (Press release, Actinium Pharmaceuticals, MAR 18, 2025, View Source [SID1234651232]). KEYTRUDA developed and commercialized by Merck & Co. and OPDIVO developed and commercialized by Bristol Myers Squibb, collectively generated $38.8 billion in sales in 2024 across several solid tumor cancer indications. However, the efficacy of these drugs has shown to be limited by a certain type of cell known as MDSCs or Myeloid Derived Suppressor Cells which accumulate in the tumor microenvironment. MDSCs express the CD33 antigen which is targeted by Actimab-A. The rationale for studying Actimab-A in combination with either KEYTRUDA or OPDIVO is based on the premise that depleting MDSCs with Actimab-A will improve the efficacy of these drugs.

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MDSCs are immune-suppressive cells that help tumors evade immune detection and promote disease progression. They are overexpressed in the tumor microenvironment in several different solid tumors and associated with poor outcomes. They work by multiple mechanisms but most relevant to PD-1 inhibitors which work by keeping T-cells active is that MDSCs prevent T-cells from recognizing and attacking cancer cells. There is considerable preclinical scientific evidence in the literature that depleting MDSCs could be a viable strategy in improving the outcomes of PD-1 directed immunotherapy, however, there have been no viable clinical approaches that have been tried successfully to our knowledge. MDSCs are known to express the CD33 antigen which is the target of Actimab-A. Actinium has also generated published and unpublished preclinical data showing that Actimab-A can selectively deplete MDSCs in solid tumors. Actinium believes that in the clinic Actimab-A can deplete CD33 expressing MDSCs and hence improve the outcomes with PD-1 inhibitors such as KEYTRUDA and OPDIVO.

Actimab-A is Actinium’s lead radiotherapeutic that delivers Actinium-225, a potent alpha-emitter radioisotope payload that can produce lethal double strand DNA breaks to kill targeted cells. Actimab-A has been studied in over 150 patients in several clinical trials in Acute Myeloid Leukemia or AML. Based on its safety and tolerability, Actimab-A is under clinical development via an NCI CRADA in the front-line AML setting with an expected registrational study in combination with CLAG-M in relapsed/refractory AML expected to initiate in 2025.

The Actimab-A solid tumor program is comprised of several controlled, head-to-head clinical trials that will evaluate the combination of Actimab-A with KEYTRUDA versus KEYTRUDA alone, and Actimab-A with OPDIVO versus OPDIVO alone. The initial tumors that are being targeted are HNSCC or Head and Neck Squamous Cell Carcinoma and NSCLC or Non-Small Cell Lung Cancer with a separate trial for each indication. The patient population for these trials will be adults with PD-L1 expression and locally advanced metastatic HNSCC or NSCLC randomized to either Actimab-A alone or Actimab-A with a specific checkpoint inhibitor. The objective of each trial would be to evaluate the safety and tolerability as well as following endpoints including ORR – Overall Response Rate, PFS – Progression Free Survival and OS – Overall Survival. Further, the following biomarker data would be collected including the pattern of depletion of CD33+ MDSCs and T-Cell activity in peripheral blood. Actinium expects to present initial proof of concept clinical data from the first of these trials in the second half of 2025 as well as provide an update on the outlook for the rest of the trials in the Actimab-A solid tumor program.

Dr. Avinash Desai, Actinium’s Chief Medical Officer, said, "The Actimab-A solid tumor program is highly novel and has the potential to address the high unmet need of patients receiving PD-1 checkpoint inhibitors whose cancer stops responding or progresses. Our preclinical data is highly encouraging and we believe this novel approach combining Actimab-A with PD-1 inhibitors has immense potential. We are greatly enthusiastic about these head-to-head trials, and eager to present our initial proof-of-concept results by the end of 2025."

Sandesh Seth, Actinium’s Chairman and CEO, said, "We have great enthusiasm for Actimab-A in combination with PD-1 checkpoint inhibitors given the large potential addressable patient population. MDSCs are over expressed in multiple solid tumors giving Actimab-A pan tumor potential in indications that are treated with checkpoint inhibitors. Per our initial estimates this represents a treatment population in excess of 500,000 patients. Together with our efforts in myeloid malignancies, this is another important program for Actimab-A. This year, clinical data from Actimab-A as a potential backbone therapy in radiation sensitive myeloid malignancies, and in solid tumors in combination with PD-1 checkpoint inhibitors, can establish its potential to become a leading blockbuster targeted radiotherapy."

On March 18, 2025 Vincerx Pharma, Inc. (Nasdaq: VINC) reported that it has entered into a non-binding letter of intent ("LOI") with Global Digital Holdings Inc., conducting business as QumulusAI, a privately-held, high-performance computing infrastructure company for artificial intelligence (AI), relating to a business combination between Vincerx and QumulusAI (Press release, Vincerx Pharma, MAR 18, 2025, View Source [SID1234651231]). The contemplated transaction would result in QumulusAI becoming a publicly traded company through a reverse triangular merger with Vincerx.

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Under the proposed terms, a subsidiary of Vincerx would merge into QumulusAI, with QumulusAI stockholders receiving shares of Vincerx common stock. Additionally, QumulusAI options, warrants, and other rights would be converted into options, warrants, and rights to acquire Vincerx common stock. The exchange ratio is intended to result in QumulusAI equity holders owning approximately 95% of the combined company, while Vincerx equity holders would own approximately 5%. The proposed transaction assumes a value for QumulusAI of approximately $285 million and a value for Vincerx of approximately $15 million, assuming zero cash (net of liabilities) at closing. As part of the transaction, to the extent requested by Vincerx, QumulusAI or its designees will invest up to $1.5 million in the equity of Vincerx prior to closing.

Following the closing of the business combination, the combined company’s board of directors would consist of seven members, all of whom would be designated by QumulusAI. QumulusAI would also determine the composition of senior management of the combined company following the closing.

The parties intend to negotiate a definitive business combination agreement that incorporates the provisions of the LOI as well as other terms and conditions typical for transactions of this nature. Conditions to execution of a definitive business combination agreement include satisfactory completion of due diligence by the parties and approval by the boards of directors of the parties. The parties have agreed to a 30-day exclusivity period to negotiate and enter into a definitive business combination agreement, which will include customary closing conditions such as board and stockholder approvals, regulatory approvals, effectiveness of a registration statement relating to the issuance of Vincerx common stock in the business combination and listing of the combined company’s common stock on Nasdaq.

"We believe this merger will allow us to create value for our stockholders by entering the AI space at a time of rapid growth," said Raquel Izumi, Ph.D., Acting Chief Executive Officer of Vincerx. "We also believe QumulusAI is well positioned to disrupt the data center space with its high-performance, energy-efficient infrastructure, addressing the escalating demand for AI compute resources. In parallel, we will continue pursuing efforts to monetize our remaining assets."

"We’re excited about a potential merger with Vincerx, a milestone we believe will accelerate QumulusAI’s mission to power the future of artificial intelligence," said Steve Gertz, Chairman of the Board. "This proposed transaction will strengthen our ability to deliver cutting-edge AI solutions with high scalability, efficiency, and reliability—essential for advancing the next generation of AI.

This transaction would bring access to public capital markets, helping to fund the growth of our High-Performance Computing as a Service (HPCaaS) bedrock and enabling QumulusAI to expand its on- and off-grid data center infrastructure. Our behind-the-meter, natural gas-powered data centers are designed to alleviate strain on the energy grid, while our HPCaaS solutions are purpose-built to meet the surging demand for AI development."

Chardan is acting as the exclusive financial advisor and Fox Rothschild is acting as legal advisor to QumulusAI.

On March 18, 2025 Pyxis Oncology, Inc. (Nasdaq: PYXS), a clinical-stage company developing next-generation therapeutics for difficult-to-treat cancers, reported financial results for the year and quarter ended December 31, 2024, and provided a business update (Press release, Pyxis Oncology, MAR 18, 2025, View Source [SID1234651230]).

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"We are committed to the development of a novel therapy for patients with recurrent or metastatic head and neck squamous cell carcinoma who will progress following platinum-based therapies and prior PD-(L)1 therapy, and those that progress after current and emerging EGFRi therapies," said Lara S. Sullivan, M.D., President and Chief Executive Officer. "We look forward to expanding upon the encouraging safety and efficacy results observed from our Phase 1 trial evaluating micvotabart pelidotin, and we believe targeting Extradomain-B Fibronectin (EDB+FN) will offer a novel approach to addressing the limitations of existing therapies."

"Given the positive micvotabart pelidotin data, it is critical that we ensure the flawless execution of our clinical programs on the fastest possible timeline," said Dr. Sullivan. "To support this goal, we have streamlined our organization to allocate resources in a way that gives us the greatest opportunity to deliver on our mission and bring meaningful therapies to patients who need them most. I am confident that our focused approach will drive value for both patients and shareholders," concluded Dr. Sullivan.

Pipeline Updates

In 2024 the Company established that its lead therapeutic candidate, micvotabart pelidotin (MICVO, formerly referred to as PYX-201), has profound monotherapy effect on multiple tumor types with significant tumor regression demonstrated during the Phase 1 dose escalation study. MICVO is a first-in-concept antibody-drug conjugate antibody-drug conjugate (ADC) that targets EDB+FN, a non-cellular structural component of the tumor extra-cellular matrix.

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Recently reported positive preliminary data from the ongoing Phase 1 dose-escalation trial of micvotabart pelidotin evaluating its safety and efficacy in multiple solid tumor types. In six heavily pretreated HPV-positive and HPV-negative efficacy evaluable patients who had received a median of four prior lines of therapy with R/M HNSCC, micvotabart pelidotin achieved a confirmed 50% objective response rate (ORR) based on RECIST 1.1 criteria, including one complete response and a disease control rate (DCR) of 100%.

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Initiated Part 2 monotherapy expansion cohorts of the ongoing Phase 1 clinical trial to evaluate micvotabart pelidotin in 2L and 3L R/M HNSCC patients who have received prior platinum and PD-1 inhibitor therapy, and 2L and 3L R/M HNSCC patients who have received prior EGFRi and PD-1 inhibitor therapy. Preliminary data from patients who have received prior platinum and PD-1 inhibitor therapy are expected in the second half of 2025 and preliminary data from patients who have received prior EGFRi and PD-1 inhibitor therapy are expected in the first half of 2026. R/M HNSCC continues to be an area of high medical need despite improvements in treatment options.

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Initiated Phase 1/2 combination study of micvotabart pelidotin and Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with R/M HNSCC and other advanced solid tumors. We aim to select a dose of micvotabart pelidotin in combination with pembrolizumab by mid-year 2025 and share preliminary data from the trial in the second half of 2025.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

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Received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for micvotabart pelidotin for the treatment of adult patients with R/M HNSCC whose disease has progressed following treatment with platinum-based chemotherapy and an anti-PD-(L)1 therapy.
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In December 2024, suspended further development of PYX-106 — a fully human IgG1 monoclonal antibody targeting Siglec-15 to allocate resources toward advancing micvotabart pelidotin.
Business Updates

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Pyxis Oncology recently announced a portfolio prioritization, focusing resources on advancing its lead clinical program, micvotabart pelidotin. In connection with the portfolio prioritization, the Company reported it has reduced its workforce by approximately 20%, with a majority of the headcount reductions from the Company’s G&A and preclinical group. In addition, Ken Kobayashi, M.D., F.A.C.P, is stepping down as Chief Medical Officer and Lara S. Sullivan, M.D., President and Chief Executive Officer will assume the role of Chief Medical Officer along with her current role as President and Chief Executive Officer.

Full Year 2024 Financial Results

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As of December 31, 2024, Pyxis Oncology had cash and cash equivalents, including restricted cash, and short-term investments, of $128.4 million. The Company believes that its current cash, cash equivalents, and short-term investments will be sufficient to fund its operations into the second half of 2026.

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Research and development expenses were $58.7 million for the year ended December 31, 2024, compared to $49.6 million for the year ended December 31, 2023. The increase was primarily due to increased clinical trial-related expenses, including manufacturing of drug product and drug substance for Phase 1 clinical trials of micvotabart pelidotin and the recently attrited PYX-106 asset.

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General and administrative expenses were $25.4 million for the year ended December 31, 2024, compared to $32.6 million for the year ended December 31, 2023. The decrease was primarily due to lower employee costs including stock-based compensation and decrease in legal, professional and consulting fees.

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During the fourth quarter of 2024, Pyxis Oncology recorded a non-cash impairment loss of $21.0 million for in-process research and development (IPR&D) intangible asset related to PYX-107, which was acquired by the Company in August 2023 as part of the acquisition of Apexigen. The impairment loss was mainly due to de-prioritization of clinical development of PYX-107. Despite the impairment loss, acquisition of Apexigen remains a net accretive transaction for the Company wherein we received $9.5 million of cash since acquisition from the sale of royalty rights and royalty payments.

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Net loss was $77.3 million, or ($1.32) per common share, for the year ended December 31, 2024, compared to $73.8 million, or ($1.85) per common share, for the year ended December 31, 2023. Excluding non-cash stock-based compensation expense and impairment loss, the net loss for the year ended December 31, 2024, was $43.4 million, compared to net loss of $56.8 million for the year ended December 31, 2023.

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As of March 17, 2025, the outstanding number of shares of Common Stock of Pyxis Oncology was 61,590,415.

On March 18, 2025 Purple biotech presented its corporate presentation (Presentation, Purple Biotech, MAR 18, 2025, View Source [SID1234651229]).

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On March 18, 2025 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported financial and operating results for the fourth quarter and full year ended December 31, 2024 (Press release, Olema Oncology, MAR 18, 2025, View Source [SID1234651228]).

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"2024 was a productive year for Olema and we closed the year with significant positive momentum. We announced a new clinical trial collaboration and supply agreement with Novartis, raised approximately $250 million through an equity private placement with high-quality, long-term investors, presented compelling data supporting palazestrant in combination with ribociclib at SABCS, received clearance from the FDA for our IND application for OP-3136, and moved quickly to begin enrolling patients in the OP-3136 Phase 1 study before the end of the year," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "Bolstered by a strong balance sheet, we are focused on exemplary execution throughout 2025. We plan to advance patient enrollment in the pivotal Phase 3 OPERA-01 trial in second- and third-line ER+/HER2- metastatic breast cancer, initiate our second pivotal Phase 3 trial, called OPERA-02, in frontline metastatic breast cancer, continue enrolling patients in the Phase 1 trial of OP-3136, present mature data from the Phase 1b/2 trial of palazestrant in combination with ribociclib, and further expand our capabilities through drug discovery and partnerships – all to help patients living with cancer feel better, longer."

Recent Progress

Presented new preclinical data demonstrating anti-tumor activity for palazestrant in combination with capivasertib and everolimus as well as new preclinical data for OP-3136 as a single agent and in combination with palazestrant and other targeted agents at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in October.
Announced a new clinical trial collaboration and supply agreement with Novartis in frontline metastatic breast cancer.
Successfully completed a $250 million equity private placement with new and existing institutional and accredited investors.
Announced intention to proceed with OPERA-02, the Company’s second pivotal Phase 3 trial, of palazestrant in combination with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib in frontline metastatic breast cancer.
Presented updated clinical results from the ongoing Phase 1b/2 study of palazestrant in combination with ribociclib in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer at the San Antonio Breast Cancer Symposium (SABCS) in December. Presented updated median progression-free survival (mPFS) from this trial at the TD Cowen 45th Annual Health Care Conference in March 2025.
Received clearance from the U.S. Food and Drug Administration (FDA) for the Investigational New Drug (IND) application for OP-3136.
Initiated the Phase 1 clinical trial for OP-3136 and began enrolling patients before year-end.
Anticipated Upcoming Events

Advance patient accrual in the pivotal Phase 3 OPERA-01 clinical trial of palazestrant as a monotherapy in second- and third-line (2/3L) metastatic breast cancer; top-line data are anticipated in 2026.
Initiate the pivotal Phase 3 OPERA-02 clinical trial of palazestrant in combination with ribociclib in frontline metastatic breast cancer.
Present new preclinical data for OP-3136.
Present mature data from the Phase 1b/2 clinical trial of palazestrant in combination with ribociclib at a medical meeting.
Fourth Quarter and Full Year 2024 Financial Results
Cash, cash equivalents, and marketable securities as of December 31, 2024, were $434.1 million.

Net loss for the quarter and year ended December 31, 2024 was $33.6 million and $129.5 million, respectively, as compared to $26.8 million and $96.7 million for the quarter and year ended December 31, 2023, respectively. The increase in net loss for the fourth quarter was primarily related to increased spending on clinical development and research activities as a result of late-stage clinical trials for palazestrant, the advancement of OP-3136, and lower interest income earned from marketable securities.

GAAP research and development (R&D) expenses were $32.3 million and $124.5 million for the quarter and year ended December 31, 2024, respectively, as compared to $25.9 million and $86.1 million for the quarterand year ended December 31, 2023. The increase in R&D expenses was primarily related to increased spending on clinical operations and development-related activities as the Company continues to advance palazestrant through late-stage clinical trials, research-related activities associated with the advancement of OP-3136, and personnel related costs, including an increase in non-cash stock-based compensation expense.

Non-GAAP R&D expenses were $27.7 million and $108.0 million for the quarter and year ended December 31, 2024, respectively, excluding $4.6 million and $16.5 million non-cash stock-based compensation expense. Non-GAAP R&D expenses were $23.0 million and $74.4 million for the quarter and year ended December 31, 2023, respectively, excluding $2.9 million and $11.8 million non-cash stock-based compensation expense, respectively. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this press release.

GAAP G&A expenses were $4.5 million and $17.7 million for the quarter and year ended December 31, 2024, respectively, as compared to $4.5 million and $18.8 million for the quarter and year ended December 31, 2023. The decrease in G&A expenses was primarily due to decreased spending on corporate-related costs, offset by an increase in non-cash stock-based compensation expense.

Non-GAAP G&A expenses were $2.8 million and $11.7 million for the quarter and year ended December 31, 2024, respectively, excluding $1.7 million and $6.0 million non-cash stock-based compensation expense, respectively. Non-GAAP G&A expenses were $3.1 million and $13.3 million for the quarter and year ended December 31, 2023, excluding $1.4 million and $5.5 million non-cash stock-based compensation expense, respectively. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this press release.