On April 26, 2025 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported updated results from its ongoing Phase 2 open-label ADVANCED-2 trial assessing intravesical TARA-002, the Company’s investigational cell-based therapy, in high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) patients with carcinoma in situ, or CIS (± Ta/T1), who are Bacillus Calmette-Guérin (BCG)-Unresponsive or BCG-Naïve (Press release, Protara Therapeutics, APR 26, 2025, View Source [SID1234652191]). The results will be featured today during an interactive poster session at the American Urological Association 2025 Annual Meeting in Las Vegas.

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"For patients with high-risk NMIBC, there are few effective and durable therapies available other than radical cystectomy, which we know is quite difficult for patients to tolerate," said Tom Jayram, M.D., Director of the Advanced Therapeutics Center at Urology Associates, and ADVANCED-2 study investigator. "TARA-002 has shown impressive efficacy, safety profile, and 12-month durability in its Phase 2 trial. In the clinic, we have seen TARA-002 become easily integrated into workflow without major hurdles for the patients or staff. This combination of clinical activity and ease of use makes me optimistic about TARA-002 having a meaningful impact in clinical practice."

Interim Results

BCG-Unresponsive Cohort

The BCG-Unresponsive dataset includes a total of five patients, all of whom were six- and nine-month evaluable, and three of whom were evaluable at 12 months as of an April 16, 2025 data cutoff.

The complete response (CR) rate at any time in BCG-Unresponsive patients was 100% (5/5).
The CR rate in BCG-Unresponsive patients was 100% (5/5) at six months, 80% (4/5) at nine months, and 67% (2/3) at 12 months.
BCG-Naïve Cohort

The BCG-Naïve dataset includes a total of 21 patients, including 16 evaluable at six months, eight at nine months, and seven at 12 months as of an April 16, 2025 data cutoff.

The CR rate at any time in BCG-Naïve patients was 76% (16/21).
The CR rate in BCG-Naïve patients was 63% (10/16) at six months, 63% (5/8) at nine months, and 43% (3/7) at 12 months.
Safety

The majority of adverse events were Grade 1 and transient with no Grade 3 or greater treatment-related adverse events (TRAEs) as assessed by study investigators. No patients discontinued treatment due to TRAEs. The most common adverse events were in line with typical responses to bacterial immunopotentiation, such as flu-like symptoms. The most common urinary symptoms reflect urinary tract instrumentation effects, such as bladder spasm, burning sensation, and urinary tract infection. Most bladder irritations resolved shortly after administration or within a few hours to a few days.

"The durable results shared today continue to support our conviction that TARA-002 has the potential to make a meaningful difference in the lives of patients with NMIBC," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "Notably, we are particularly pleased with the competitive 12-month CR rates observed in the registrational BCG-Unresponsive cohort as well as the BCG-Naïve cohort. We look forward to continuing to advance this important trial as we work toward our mission of bringing transformative therapies to patients."

The Company continues to expect to present an interim update with results from approximately 25 six-month evaluable BCG-Unresponsive patients by the end of 2025.

Conference Call and Webcast

Protara will host a conference call and webcast to discuss the data on Monday, April 28, 2025, at 8:30 am ET. The live call can be accessed by registering as a participant here. Upon registration, participants will receive conference call dial-in information. A live webcast of the event can be accessed by visiting the Events and Presentations section of the Company’s website: View Source The webcast will be archived for a limited time following the presentation.

About ADVANCED-2

ADVANCED-2 (NCT05951179) is a Phase 2 open-label trial assessing intravesical TARA-002 in NMIBC patients with carcinoma in situ or CIS (± Ta/T1) who are Bacillus Calmette-Guérin (BCG)-Unresponsive (n≈100) and BCG-Naïve (n=31). The BCG-Unresponsive cohort has been designed to be registrational in alignment with the U.S. Food and Drug Administration’s 2024 BCG-Unresponsive Non-muscle Invasive Bladder Cancer: Developing Drugs and Biological Products for Treatment, Draft Guidance for Industry.

About TARA-002

TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of LMs, for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432.

When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a pro-inflammatory response with release of cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma IL-6, IL-10, IL-12. TARA-002 also directly kills tumor cells and triggers a host immune response by inducing immunogenic cell death, which further enhances the antitumor immune response.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

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