On April 25, 2025, United Therapeutics Corporation (the "Company") entered into a Credit Agreement (the "Credit Agreement") with the lenders referred to therein and Wells Fargo Bank, National Association ("Wells Fargo"), as administrative agent and as a swingline lender (Filing, 8-K, United Therapeutics, APR 25, 2025, View Source [SID1234652250]). The Credit Agreement provides for an unsecured, revolving credit facility of up to $2.5 billion (which facility may, subject to obtaining commitments from existing or new lenders for such increase and subject to other condition, be increased by up to $750 million in the aggregate). The facility matures five years after the closing date of the Credit Agreement, subject to an ability of the lenders thereunder, or certain of the lenders thereunder, to elect to extend the maturity date of their commitments by one year following a request for such extension by the Company in accordance with the terms of the Credit Agreement, up to a maximum of two such extensions.

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As of April 25, 2025, there are no subsidiaries of the Company required to be a guarantor and guarantee the Company’s obligations under the Credit Agreement. From time to time, one or more subsidiaries of the Company may be required to guarantee the Company’s obligations under the Credit Agreement.

At the Company’s option, the loan will bear interest at either an adjusted Term SOFR rate or a fluctuating base rate, in each case, plus an applicable margin that is determined on a quarterly basis based on the Company’s consolidated total leverage ratio (as calculated in accordance with the Credit Agreement).

The proceeds of borrowings under the Credit Agreement are available to refinance certain existing indebtedness of the Company and its subsidiaries and/or for working capital and other general corporate purposes. Upon closing of the Credit Agreement on April 25, 2025, the Company borrowed $200.0 million under the Credit Agreement, and used the funds to repay outstanding indebtedness under the 2022 Credit Agreement discussed under Item 1.02 below.

The Credit Agreement also contains customary affirmative and negative covenants that, among other things, limit the ability of the Company and its subsidiaries to (a) in the case of subsidiaries that are not guarantors of the credit facility, incur indebtedness; (b) grant liens; (c) solely with respect to credit parties under the credit facility, enter into a merger, consolidation or amalgamation; (d) liquidate, wind up or dissolve; or (e) sell all or substantially all of the property, business or assets of the Company and its subsidiaries taken as a whole. In addition, as of the last day of each fiscal quarter, the Company must not permit a consolidated ratio of total indebtedness to EBITDA to be greater than 3.50 to 1.00 (which ratio may, upon consummation of (i) certain qualifying acquisitions, be increased to 4.00 to 1.00 for four fiscal quarters following such acquisition and (ii) certain qualifying inbound licensing transactions, be increased to 4.00 to 1.00 for the first two fiscal quarters following such inbound licensing transaction and 3.75 to 1.00 for the next two fiscal quarters following such inbound licensing transaction) and its consolidated interest coverage ratio to be less than 3.00 to 1.00, in each case calculated in accordance with the Credit Agreement.

The Credit Agreement contains customary events of default, including a change of control. Upon the occurrence and continuation of an event of default, all amounts due under the Credit Agreement and the other loan documents become (in the case of a bankruptcy event), or may become (in the case of all other events of default and at the option of the lenders), immediately due and payable.

The foregoing summary is qualified in its entirety by reference to the copy of the Credit Agreement attached hereto as Exhibit 10.1.

On April 25, 2025, Bullfrog AI Holdings, Inc. (the "Company") entered into an At-The-Market Sales Agreement (the "Agreement") with BTIG, LLC ("BTIG"), pursuant to which the Company may offer and sell, from time to time in its sole discretion, shares of its common stock, par value $0.00001 per share (the "Common Stock"), having an aggregate offering price of up to $20,000,000 (the "Shares"), through BTIG as its sales agent (Filing, 8-K, Bullfrog AI, APR 25, 2025, View Source [SID1234652222]). The Shares will be offered and sold pursuant to the Company’s Registration Statement on Form S-3 (Registration No. 333-281341) filed by the Company on August 7, 2024, as amended by Amendment No. 1 thereto filed on August 15, 2024, and declared effective by the U.S. Securities and Exchange Commission on August 21, 2024 (the "Registration Statement") and the Company’s prospectus supplement filed on April 25, 2025 that forms a part of such Registration Statement. The issuance and sale, if any, of the Shares may be made by any method permitted by law deemed to be an "at-the-market offering" as defined in Rule 415 of the Securities Act of 1933, as amended, including, without limitation, sales made directly on the Nasdaq Capital Market, or on any other existing trading market for the Common Stock.

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The Company is not obligated to make any sales of the Common Stock, and BTIG is not required to sell any specific number or dollar amount of shares of the Common Stock, under the Agreement. The Company and BTIG may suspend or terminate the offering of Shares upon notice to BTIG or the Company, as applicable, and subject to other conditions.

Subject to the Company’s request to sell Shares, BTIG will act as the Company’s sales agent and use commercially reasonable efforts, consistent with its normal trading and sales practices, to sell on the Company’s behalf, from time to time, such Shares based upon instructions from the Company (including any price, time or size limits or other customary parameters or conditions that the Company may impose). The Company will pay BTIG a commission fee of 3% of the gross sales price of any Shares sold through BTIG under the Agreement, and also has provided BTIG with customary representations and warranties and indemnification under the Agreement.

The foregoing description of the Agreement is not complete and is qualified in its entirety by reference to the full text of the Agreement, a copy of which is filed as Exhibit 1.1 to this Current Report on Form 8-K and incorporated herein by reference. The opinion of Ballard Spahr regarding the validity of the Shares that will be issued pursuant to the Agreement is also filed herewith as Exhibit 5.1.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation, or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

On April 25, 2025 Onc.AI, a digital health company developing advanced AI-driven clinical management solutions for oncology, reported that findings from a recent collaboration with global biopharma company GSK using Onc.AI’s FDA breakthrough-designated Serial CTRS AI model will be presented at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Onc AI, APR 25, 2025, View Source [SID1234652184]). The study externally evaluated Serial CTRS in GSK’s GARNET Phase I clinical trial (NCT02715284) Cohort E, that enrolled patients with advanced non-small cell lung cancer (NSCLC) treated with dostarlimab, GSK’s anti-PD-1 checkpoint inhibitor.

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Results, highlighted in a poster presentation during the Predictive Biomarkers 2 session (poster #21, April 27, 2025, 2-5pm), demonstrated that the Serial CTRS biomarker, leveraging routine CT imaging without manual annotations, improved prediction of overall survival (OS) compared to traditional surrogates including RECIST 1.1 response criteria and tumor volume. The analysis was conducted through an independent and blinded retrospective validation study carried out by GSK. In particular, Serial CTRS showed the ability to distinguish patients with intermediate versus high probabilities of 12-month OS (HR: 2.91, 95% CI: 1.16–7.31), outperforming RECIST 1.1 (HR: 1.34, 95% CI: 0.57–3.13) and tumor volume change assessments (HR: 1.00, 95% CI: 0.43–2.34). This enhanced predictive performance supports Onc.AI’s commitment to establishing Serial CTRS as a new standard for automated, AI-based imaging endpoints in the early assessment of treatment response, seamlessly integrating into standard imaging workflows across diverse therapeutic regimens.

Key findings include:

Serial CTRS improved discrimination between intermediate and high probabilities of overall survival compared to RECIST 1.1 and tumor volume changes.
Serial CTRS remained a significant predictor of overall survival after adjusting for known prognostic factors, such as age, baseline tumor volume, and PD-L1 Tumor Proportion Score (TPS).
"This important milestone for Serial CTRS builds on a recent breakthrough-designation from FDA," said Akshay Nanduri, CEO of Onc.AI. "The success of this validation study and ongoing continued collaboration with GSK reflects the strength and robustness of model performance. This can only be achieved using advanced Deep Learning combined with methods for harmonizing diverse imaging data and the breadth of our training data. Onc.AI’s high-quality data on thousands of patients has been sourced from dozens of healthcare systems representing hundreds of clinics across the United States and other international cancer centers, ensuring unparalleled diversity in training, test and validation."

"As the past head of multiple Phase I clinics at top cancer centers, I believe that Onc.AI’s innovation with Serial CTRS could transform the pharma clinical development process from Phase I to Phase III studies," said George R. Simon, MD, FACP, FCCP, Vice President of Oncology at OhioHealth.

On April 25, 2025 Iksuda Therapeutics (Iksuda), the developer of class leading, clinically validated antibody drug conjugates (ADCs) reported that it will present three posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois (25-30 April) (Press release, Iksuda Therapeutics, APR 25, 2025, View Source [SID1234652182]). The posters cover the Company’s new payload class, the ProAlk series, its CA242-directed ADC, IKS04, being developed for the treatment of gastrointestinal (GI) cancers, and its proprietary PermaLink conjugation chemistry.

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Iksuda will introduce its new ProAlk payload class which has a novel protein alkylating mechanism and is incorporated in ADCs in a prodrug format for enhanced targeting precision. ProAlk is active across a broad range of tumours and has been designed for optimal ADC relevance. It is associated with potent bystander activity and is MDR-resistant. Its novel mechanism will help to address the growing and significant challenge of ADC sequencing, where differentiation from tubulin and topoisomerase I inhibitor payloads will become imperative. Iksuda is building a pipeline of ProAlk driven ADCs which incorporate its proprietary PermaLink conjugation chemistry for ADC stability and tumour-selective payload activation and release for enhanced precision and safety.

The Company will also present a poster on IKS04, its CA242-directed ADC for the treatment of GI cancers and which is in IND-enabling studies. IKS04 uses a pro-drug approach for the tumour-specific delivery of a highly potent pyrrolobenzodiazepine (PBD) payload, avoiding the typical toxicity profile seen in traditional PBD ADCs. In preclinical trials, IKS04 is associated with in vivo efficacy which is substantially improved over benchmark ADCs in all tumour models, and a superior therapeutic index over all other PBD-based solid tumour ADC programs. IKS04 will be administered via pre-administration of naked antibody – a novel dosing regimen in the ADC field – to overcome high expression abundance and enable higher tumour penetration and consistent levels of efficacy across tumours. IKS04 is expected to enter clinical development in GI cancers by the end of 2025.

In addition, Iksuda will highlight its proprietary PermaLink conjugation chemistry, which is used across its early-stage ADC platform alongside the Company’s glucuronide linker formats and novel ProAlk payload. PermaLink offers a simple, scalable and highly stable bioconjugation method as an alternative to maleimide-based conjugation, enabling highly stable ADCs with favourable anti-tumour activity and safety.

Dr Dave Simpson, Chief Executive Officer, Iksuda Therapeutics, said:

"These three poster presentations at AACR (Free AACR Whitepaper) demonstrate Iksuda’s leadership in ADC innovation as we unveil our novel ProAlk payload class, overcoming the challenges in ADC sequencing and which will drive Iksuda’s deepening pipeline. With two clinical-stage programs, a growing pipeline of class leading ADCs and our expanding, innovative platforms, we are strongly positioned to progress new and promising ADCs to deliver improved outcomes for patients living with cancer. We look forward to progressing IKS04 into clinical development for GI cancers later this year, an area of high unmet need with limited effective treatment options and poor five-year survival rates for the significant number of patients with advanced disease."

Poster Presentation details:

ProAlk

Abstract Title:

PA289, a prodrug linker-payload with a novel mechanism of action for the development of antibody drug conjugates

Session Title:

Antibody-Based Cancer Therapeutics 1

Date/Time:

April 28, 2025 9:00 AM – 12:00 PM

Location:

Poster Section 15

Poster Number:

1579/28

IKS04

Abstract Title:

IKS04, an antibody drug conjugate with a highly potent DNA crosslinker payload for the treatment of gastrointestinal cancers

Session Title:

Antibody-Based Cancer Therapeutics 2

Date/Time:

April 28, 2025 2:00 PM – 5:00 PM

Location:

Poster Section 15

Poster Number:

2885/24

PermaLink

Abstract Title:

PermaLink, a stable and scalable bioconjugation platform as an alternative to maleimide-based conjugation

Session Title:

Antibody-Based Cancer Therapeutics 1

Date/Time:

April 28, 2025 9:00 AM – 12:00 PM

Location:

Poster Section 15

Poster Number:

1570/19

On April 25, 2025 NextPoint Therapeutics, a clinical-stage biotechnology company launching a new world of precision therapeutics through its leading scientific work on the novel B7-H7 axis, reported it will present compelling data on NPX125, its lead B7-H7-targeting antibody-drug conjugate (ADC) with a proprietary novel linker technology, at the American Association for Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago (Press release, NextPoint Therapeutics, APR 25, 2025, View Source [SID1234652181]).

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NPX125, which utilizes NextPoint’s proprietary linker technology paired with a clinically validated topoisomerase 1 inhibitor payload in a DAR8 (drug-antibody ratio) format, is initiating IND-enabling work with an anticipated IND filing in mid-2026. Leveraging B7-H7’s superb internalization profile that enables efficient payload delivery, the company expects this first-in-class ADC targeting B7-H7 to enter the clinic shortly thereafter, expanding NextPoint’s multimodal approach to targeting the B7-H7 axis.

Poster Details
Title: B7-H7 is a novel ADC target for solid tumors and shows potent activity with multiple payload-linker technologies
Abstract Number: 7336
Section: 40
Session Date/Time: Wednesday, April 30, 2025, 9:00 AM – 12:00 PM

"The data we’re presenting at AACR (Free AACR Whitepaper) validate the B7 family as an outstanding ADC target with a highly favorable profile compared to other clinically successful targets and even members of the B7 family, like B7-H3 and B7-H4," said Tatiana Novobrantseva, PhD, Chief Scientific Officer at NextPoint Therapeutics. "NPX125 emerged as the lead candidate among multiple B7-H7-targeting ADCs tested, and has demonstrated remarkable internalization kinetics, potent cytotoxicity and strong anti-tumor activity across tumor models with varying levels of B7-H7 expression, supporting our conviction in its potential to deliver meaningful benefits to patients."

Key Program Attributes include:

Superior ADC Properties
NPX125 via its interaction with B7-H7 demonstrated efficient internalization across many different tumor cell lines
Showed both direct and bystander cytotoxic activity, critical for addressing tumor heterogeneity
NPX125 demonstrated superior serum stability in rat pharmacokinetic studies
Robust developability profile due to antibody selection and unique linker properties
Strong Anti-Tumor In Vivo Efficacy
NPX125 achieved tumor regressions in multiple preclinical mouse models with variable B7-H7 expression levels
Additional Poster Presentations at AACR (Free AACR Whitepaper)
NextPoint will also present three additional posters at AACR (Free AACR Whitepaper) showcasing its comprehensive approach to targeting the B7-H7 axis:

"B7-H7-CD3 bispecific T cell engaging antibodies demonstrate potent anti-tumor activity in B7-H7+ preclinical tumor models" (Abstract #1556)
"Comprehensive analysis of B7-H7/HHLA2 expression in pan-solid tumors and its potential significance in anti-tumor immunity" (Abstract #3302)
"Safety and tolerability of NPX372, a novel B7-H7 bispecific T cell engaging antibody" (Abstract #4354)
The poster presentations are available in the "News & Publications" section of NextPoint’s website: View Source

About B7-H7
B7-H7 (also known as HHLA2) represents an ideal tumor-targeting antigen, with limited normal tissue expression and upregulation on a broad range of solid tumor histologies. Unlike other B7 family members which may be expressed on tumor cells and immune cell populations, B7-H7 expression is detectable only on tumor epithelial cells, which makes it a more specific tumor-targeting antigen. B7-H7’s expression across multiple tumor types, coupled with its role in immunomodulation in the tumor microenvironment, positions it as a promising target for precision therapeutic approaches.