Plus Therapeutics Secures $5.7 Million Financing to Support Leptomeningeal Metastases Program

On February 18, 2025 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company," or "Plus Therapeutics"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, reported that it has closed a private placement with aggregate initial upfront proceeds of approximately $3.7 million and received a $2.0 million advance payment from CPRIT as part of its existing $17.6 million grant award (Press release, Plus Therapeutics, FEB 18, 2025, View Source [SID1234650348]). The funding from the private placement and the CPRIT advance will support the Company’s clinical development of Rhenium (186Re) Obisbemeda for leptomeningeal metastases (LM), as well as further development of the Company’s CNSide LM diagnostic test as a pivotal trial endpoint.

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"We are grateful for the enthusiasm and ongoing support from both existing investors and key funding agencies, including CPRIT, the National Institutes of Health, and the U.S. Department of Defense," said Marc H. Hedrick, M.D., Plus Therapeutics’ President and Chief Executive Officer. "This capital, along with expected grant allocations later in 2025, is expected to fully support the completion of two planned LM trials, strategically positioning the company for a pivotal trial in 2026."

Private Placement Financing

The private placement comprised the issuance and sale of secured convertible promissory notes, or Funding Notes, in the aggregate amount of $3,362,251 and common stock purchase warrants to purchase up to an aggregate of 3,002,009 shares of the Company common stock at an exercise price of $1.12 per share. The notes have a maturity date of one year from the closing of the financing and are convertible in future financings of the Company or into common stock at the election of the investors. The financing includes participation from AIGH Capital Management LLC with additional participation from existing healthcare-focused institutional investors.

The accompanying Warrants will be exercisable until the five-year anniversary of the closing of the financing.

The Notes are convertible, under certain circumstances, to shares of common stock of the Company at an exercise price of $1.12 per share. The Notes are senior, secured obligations of the Company. The Notes bear interest at the rate of ten percent (10%) per annum, payable on the last business day of each quarter, except as provided therein.

The gross proceeds to the Company from the private placement were approximately $3.7 million, before deducting offering expenses payable by the Company. The Company currently intends to use the net proceeds from the private placement for general corporate and working capital purposes.

The securities offered in the private placement and described above were offered in transactions not involving a public offering under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act") and/or Rule 506(b) of Regulation D promulgated thereunder and have not been registered under the Securities Act or applicable state securities laws. Accordingly, the securities in the private placement may not be reoffered or resold in the United States except pursuant to an effective registration statement with the SEC or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

This press release does not constitute an offer to sell or the solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state. Any offering of the securities under the resale registration statement will only be made by means of a prospectus.

CPRIT Funding Advance

In addition to the $3.7 million private placement financing from existing investors, the Company announced a $2.0 million advance payment from CPRIT as part of its existing $17.6 million grant award. The funding will support and accelerate the Company’s clinical development of Rhenium (186Re) Obisbemeda for the ReSPECT-LM P2a single-dose expansion trial and further develop the Company’s CNSide LM diagnostic test as a key pivotal trial endpoint.

To date, the Company has received multiple disbursements under its CPRIT grant. Following this $2.0 million advance payment, approximately $5.2 million remains from the original $17.6 million grant award.

Exchange and Financing Waiver

On February 13, 2025, the Company also issued secured convertible promissory notes, or Exchange Notes, in the aggregate amount of $3,188,922 in exchange for existing investors agreeing to cancel 3,543,247 Series A common stock purchase warrants issued by the Company in May 2024 and waive certain existing restrictions on the Company’s ability to raise capital. The terms of the Exchange Notes are substantially similar to the terms of the Funding Notes.

Additional information on the terms of the Funding Notes, Warrants, Exchange Notes and related matters can be found in the Company’s Current Report on Form 8-K that is being filed by the Company on February 18, 2025.

About Leptomeningeal Metastases (LM)

LM is a rare complication of cancer in which the primary cancer spreads to the cerebrospinal fluid (CSF) and leptomeninges surrounding the brain and spinal cord. All malignancies originating from solid tumors, primary brain tumors, or hematological malignancies have this LM complication potential with breast cancer as the most common cancer linked to LM, with 3-5% of breast cancer patients developing LM. Additionally, lung cancer, GI cancers and melanoma can also spread to the CSF and result in LM. LM occurs in approximately 5% of people with cancer and is usually terminal with 1-year and 2-year survival of just 7% and 3%, respectively. The incidence of LM is on the rise, partly because cancer patients are living longer and partly because many standard chemotherapies cannot reach sufficient concentrations in the spinal fluid to kill the tumor cells, yet there are no FDA-approved therapies specifically for LM patients, who often succumb to this complication within weeks to several months, if untreated.

About Rhenium (186Re) obisbemeda

Rhenium (186Re) obisbemeda is a novel injectable radiotherapy specifically formulated to deliver direct targeted high dose radiation in CNS tumors in a safe, effective, and convenient manner to optimize patient outcomes. Rhenium (186Re) obisbemeda has the potential to reduce off target risks and improve outcomes for CNS cancer patients, versus currently approved therapies, with a more targeted and potent radiation dose. Rhenium-186 is an ideal radioisotope for CNS therapeutic applications due to its short half-life, beta energy for destroying cancerous tissue, and gamma energy for real-time imaging. Rhenium (186Re) obisbemeda is being evaluated for the treatment of recurrent glioblastoma and leptomeningeal metastases in the ReSPECT-GBM and ReSPECT-LM clinical trials. ReSPECT-GBM is supported by an award from the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), and ReSPECT-LM is funded by a three-year $17.6M grant by the Cancer Prevention & Research Institute of Texas (CPRIT).

Petosemtamab granted Breakthrough Therapy designation by the U.S. FDA for 1L PD-L1 positive head and neck squamous cell carcinoma

On February 18, 2025 Merus N.V. (Nasdaq: MRUS), a clinical-stage oncology company developing innovative, full-length multispecific antibodies and antibody drug conjugates (Biclonics, Triclonics and ADClonics), for cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation (BTD) to petosemtamab in combination with pembrolizumab for the first-line treatment of adult patients with recurrent or metastatic programmed death-ligand 1 (PD-L1) positive head and neck squamous cell carcinoma (r/m HNSCC) with combined positive score (CPS) ≥ 1 (Press release, Merus, FEB 18, 2025, View Source [SID1234650347]).

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This second BTD designation follows the initial receipt of BTD and Fast Track designation for petosemtamab for the treatment of patients with r/m HNSCC whose disease has progressed following treatment with platinum-based chemotherapy and an anti-programmed cell death protein 1 (anti-PD-1) antibody announced in May 2024 and August 2023, respectively.

BTD is supported by updated data from the ongoing phase 1/2 open-label, multicenter trial evaluating petosemtamab in combination with pembrolizumab in 1L HNSCC expressing PD-L1 (CPS≥1) (NCT03526835). Data for this cohort was initially presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2024, which demonstrated a 67% response rate among 24 evaluable patients. The oral presentation was detailed in our press release, Merus’ Petosemtamab in Combination with Pembrolizumab Interim Data Demonstrates Robust Response Rate and Favorable Safety Profile in 1L r/m HNSCC (May 28, 2024). In the BTD application, Merus provided updated interim clinical data on efficacy, durability and safety of the cohort of petosemtamab with pembrolizumab in 1L PD-L1+ r/m HNSCC.

"We believe petosemtamab’s second BTD continues to validate its potential to become a new standard of care for patients with r/m HNSCC and underscores our commitment to accelerate development of petosemtamab for these patients," said Fabian Zohren, M.D., Ph.D., Chief Medical Officer of Merus. "Importantly, this designation indicates the interim clinical data we shared with the FDA demonstrates petosemtamab’s potential for substantial improvement over available therapies in the 1L PD-L1+ setting."

BTD is intended to expedite the development and review of a medicine to treat a serious or life-threatening condition, where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on clinically significant endpoints over available therapies. BTD allows for more intensive FDA guidance on an efficient drug development program, an organizational commitment involving senior managers, and experienced review staff, as appropriate, in a collaborative, cross-disciplinary review, and eligibility for rolling review and priority review. With this BTD, Merus plans to engage in these discussions with the FDA in an expedited manner as we move toward our goal of a potential Biologics License Application (BLA) submission.

About LiGeR-HN1
LiGeR-HN1, a phase 3 trial, will evaluate the safety and efficacy of petosemtamab in combination with pembrolizumab, compared to pembrolizumab in 1L PD-L1+ r/m HNSCC patients. The trial is open to adult patients eligible to receive pembrolizumab as 1L monotherapy with tumors expressing PD-L1, CPS ≥1. The primary endpoints are overall response rate as assessed by BICR based on RECIST v1.1 and overall survival. Secondary endpoints are duration of response and progression free survival. Merus plans to enroll approximately 500 patients in the trial.

About LiGeR-HN2
LiGeR-HN2, a phase 3 trial, will evaluate the safety and efficacy of petosemtamab compared to investigator’s choice of methotrexate, docetaxel, or cetuximab in 2/3L r/m HNSCC patients. The trial is open to adult patients that have progressed on or after anti-PD-1 therapy and platinum-containing therapy. The primary endpoints are overall response rate as assessed by BICR based on RECIST v1.1 and overall survival. Secondary endpoints are duration of response and progression free survival. Merus plans to enroll approximately 500 patients in the trial.

About Head and Neck Cancer
Head and neck squamous cell carcinoma (HNSCC) describes a group of cancers that develop in the squamous cells that line the mucosal surfaces of the mouth, throat, and larynx. These cancers begin when healthy cells change and grow in an unchecked manner, ultimately forming tumors. HNSCC is generally associated with tobacco consumption, alcohol use and/or HPV infections, depending on where they develop geographically. HNSCC is the sixth most common cancer worldwide and it is estimated that there were more than 930,000 new cases and over 465,000 deaths from HNSCC globally in 2020.1 The incidence of HNSCC continues to rise and is anticipated to increase by 30% to more than 1 million new cases annually by 2030.2 HNSCC is a serious and life-threatening disease with poor prognosis despite currently available standard of care therapies.

About Petosemtamab
Petosemtamab, or MCLA-158, is a Biclonics low-fucose human full-length IgG1 antibody targeting the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). Petosemtamab is designed to exhibit three independent mechanisms of action including inhibition of EGFR-dependent signaling, LGR5 binding leading to EGFR internalization and degradation in cancer cells, and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity.

Sonnet BioTherapeutics Selected for Poster Presentation at the 2025 AACR IO Conference

On February 18, 2025 Sonnet BioTherapeutics Holdings, Inc. (the "Company" or "Sonnet") (NASDAQ: SONN), a clinical-stage company developing targeted immunotherapeutic drugs, reported its abstract has been accepted for poster presentation at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) IO Conference taking place on February 23-26, 2025 at the JW Marriott in Los Angeles, CA (Press release, Sonnet BioTherapeutics, FEB 18, 2025, View Source [SID1234650346]).

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Details of the poster presentation are as follows:

Session: Poster Session B
Abstract title: Combination immunotherapy with an albumin-binding interleukin-12 fusion protein that extends cytokine half-life, targets the tumor microenvironment, and enhances therapeutic efficacy
Session Date and Time: Tuesday, February 25, 2025 from 1:45-4:45 PM PT

For more information about the conference, please visit the event website.

Cartesian Therapeutics to Participate in Upcoming Investor Conferences

On February 18, 2025 Cartesian Therapeutics, Inc. (NASDAQ: RNAC) (the "Company"), a clinical-stage biotechnology company pioneering mRNA cell therapies for autoimmune diseases, reported that its management expects to participate in the following investor conferences in February and March (Press release, Cartesian Therapeutics, FEB 18, 2025, View Source [SID1234650345]):

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A fireside chat at the H.C. Wainright & Co. 3rd Annual Cell Therapy Virtual Conference at 1:00 p.m. ET on Tuesday, February 25, 2025
A presentation at the TD Cowen 45th Annual Health Care Conference at 1:50 p.m. ET on Monday, March 3, 2025 in Boston, MA
A fireside chat at the Leerink Global Healthcare Conference at 8:40 a.m. ET on Monday, March 10, 2025 in Miami, FL
A live webcast of the presentation and fireside chats is expected to be accessible in the Events section of the Company’s website at www.cartesiantherapeutics.com, where an archived replay of the events will also be available for a limited time.

ORIC® Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Operational Updates

On February 18, 2025 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported financial results and operational updates for the quarter and year ended December 31, 2024 (Press release, ORIC Pharmaceuticals, FEB 18, 2025, View Source [SID1234650341]).

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"2024 was a year of significant advancements across several areas," stated Jacob M. Chacko, M.D., president and chief executive officer. "Key achievements included initiation of multiple cohorts for ORIC-114 in non-small cell lung cancer and ORIC-944 in metastatic castration-resistant prostate cancer. We also established three strategic partnerships with major pharmaceutical companies, expanded our leadership team’s expertise, and secured $125 million in financing, which extends our cash runway into late 2026. We anticipate seven data readouts in the next year and a half and are working towards potential registration studies for ORIC-114 in the latter half of 2025 and for ORIC-944 in early 2026."

2024 Key Accomplishments

ORIC-114: a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor

Entered into a clinical trial collaboration and supply agreement with Johnson & Johnson to evaluate ORIC-114 in combination with subcutaneous (SC) amivantamab for the 1L treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations.
Initiated a cohort to evaluate ORIC-114 monotherapy for the 1L treatment of patients with NSCLC harboring EGFR exon 20 insertion mutations.
Announced the completion of the dose escalation portion of the Phase 1b trial of ORIC-114 and the selection of two provisional recommended phase 2 doses; after which, initiated dosing of patients across three expansion cohorts in the Phase 1b trial of ORIC-114 in patients with mutated NSCLC, including 2L EGFR exon 20 insertion (EGFR exon 20 inhibitor naïve), 2L+ HER2 exon 20 insertion, and 2L+ EGFR atypical mutations.
Presented preclinical data demonstrating potential best-in-class properties, including potency and selectivity, of ORIC-114 to treat NSCLC harboring EGFR exon 20 insertion mutations and other atypical EGFR mutations at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics.
ORIC-944: a potent and selective allosteric inhibitor of PRC2

Reported encouraging early safety and efficacy data in ongoing dose escalation trial for ORIC-944 in combination with apalutamide in patients with metastatic castration resistant prostate cancer (mCRPC).
Initiated dosing of ORIC-944 in combination with ERLEADA (apalutamide) and in combination with NUBEQA (darolutamide) in mid-2024 in the ongoing Phase 1b trial for prostate cancer.
Entered into clinical trial collaboration and supply agreements with Johnson & Johnson and Bayer to support the ongoing Phase 1b trial of ORIC-944 in combination with AR inhibitors for the treatment of mCRPC.
Reported initial Phase 1b single agent data for ORIC-944 in metastatic prostate cancer supporting advancement into combination development and demonstrating the potential as a best-in-class PRC2 inhibitor, including a clinical half-life of ~20 hours, robust target engagement, no signs of CYP autoinduction that was observed with first-generation PRC2 inhibitors, and a generally well-tolerated safety profile.
Presented preclinical data at the 2024 AACR (Free AACR Whitepaper) Annual Meeting demonstrating superior drug properties and synergy data in prostate cancer models, reinforcing the promise of ORIC-944 as a potential best-in-class treatment for combination with AR inhibitors.
Corporate Highlights:

Strengthened cash position and runway with a $125 million private placement financing from new and existing healthcare specialist funds.
Expanded the leadership team with the appointment of industry veteran Keith Lui as Senior Vice President of Commercial and Medical Affairs.
Anticipated Program Milestones

ORIC anticipates the following upcoming data milestones:

ORIC-114 (NSCLC):
1H 2025: 2L EGFR exon 20 and 2L+ HER2 exon 20
2H 2025: 2L+ EGFR atypical
1H 2026: 1L EGFR exon 20
Mid-2026: 1L EGFR exon 20 combination with SC amivantamab and 1L EGFR atypical
ORIC-944 (mCRPC):
4Q 2025 / 1H 2026: Combination with AR inhibitors
Fourth Quarter and Full Year 2024 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $256 million as of December 31, 2024, which is expected to fund the current operating plan into late 2026.
R&D Expenses: Research and development (R&D) expenses were $32.0 million for the three months ended December 31, 2024, compared to $24.5 million for the three months ended December 31, 2023, an increase of $7.5 million. For the year ended December 31, 2024, R&D expenses were $114.1 million compared to $85.2 million for the same period in 2023, an increase of $28.9 million. The increases were due to a net increase in external expenses related to the advancement of product candidates, as well as higher personnel costs, including additional non-cash stock-based compensation.
G&A Expenses: General and administrative (G&A) expenses were $7.6 million for the three months ended December 31, 2024, compared to $6.9 million for the three months ended December 31, 2023, an increase of $0.7 million. For the year ended December 31, 2024, G&A expenses were $28.8 million compared to $25.6 million for the same period in 2023, an increase of $3.2 million. The increases were primarily due to higher personnel costs, including additional non-cash stock-based compensation.