On February 13, 2025 Bio-Path Holdings, Inc., (NASDAQ:BPTH), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer and obesity drugs, reported an update from the Company’s ongoing Phase 1/1b clinical trial of BP1001-A in solid tumor patients and reports continued patient progress from the Company’s ongoing Phase 2 triple combination study of prexigebersen in Acute Myeloid Leukemia (AML) (Press release, Bio-Path Holdings, FEB 13, 2025, View Source [SID1234650243]).

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"These continued positive responses mark a significant milestone for Bio-Path as they suggest our DNAbilize platform technology has the potential to produce multiple drug candidates capable of target-specific protein inhibition for over-expressed, disease-causing gene products," said Peter H. Nielsen, President and Chief Executive Officer of Bio-Path. "As previously reported in August 2024, we were thrilled to see that our first patient treated with the higher dose (90 mg/m2) in our Phase 1/1b study of BP1001-A who has shown tumor regression and stable disease continued successful treatment through a tenth treatment cycle. We believe this is significant, particularly considering the heavily pretreated and fragile patient population involved."

"This elderly female patient with gynecologic cancer had previously been treated with multiple lines of chemotherapy along with multiple surgeries for her disease, and only now is showing positive clinical results with BP1001-A treatment. Importantly, we are not seeing the onerous side effects typically seen in patients with advanced solid tumors being treated with standard chemotherapies," continued Mr. Nielsen.

"In addition, we previously noted extended treatment durability in two elderly patients in our Phase 2 triple combination study of prexigebersen, venetoclax and decitabine in AML patients. We are pleased to report that each of these patients remain in complete remission after two years of treatment. These ongoing positive outcomes underscore the potential for prexigebersen to treat fragile AML patients for extended periods. We are particularly pleased with these results, as elderly AML patients are typically unable to tolerate intensive chemotherapy and thus experience very poor clinical outcomes," concluded Mr. Nielsen.

Solid Tumor Patient Response in Second, Higher Dose Cohort – Previously, Bio-Path reported its first patient in the second dose cohort in its Phase 1/1b advanced solid tumor clinical trial experienced a positive response that may signal that this analog of prexigebersen has potential as a new treatment for advanced solid tumors. The patient appears to be doing well on study after failing extensive chemotherapy and surgical treatment for gynecologic cancer, demonstrating a 15% reduction in her primary tumor through six cycles of treatment. Moreover, it appears that these positive outcomes may have contributed to allowing her to continue with rigorous exercise and improved quality of life.

As of January 2025, this patient continues doing well on treatment, recently completing nine cycles and is now in her tenth treatment cycle.

The dose finding portion of the Phase 1/1b trial is comprised of BP1001-A monotherapy with no accompanying chemotherapy. This clinical trial of BP1001-A in patients with advanced or recurrent solid tumors has successfully completed the initial prescribed dose in the first cohort of 60 mg/m2 and began enrollment in the higher dose cohort of 90 mg/m2. The Phase 1b portion of the study is expected to commence after completion of three planned BP1001-A monotherapy dose level cohorts and is intended to assess the safety and efficacy of BP1001-A in combination with paclitaxel in patients with recurrent ovarian or endometrial tumors. Phase 1b studies are also expected to be opened in combination with gemcitabine in late-stage pancreatic cancer.

AML Patients Demonstrate Extended Treatment Durability – Previously, Bio-Path reported two patients were identified in the Phase 2 clinical trial treating AML patients who demonstrated continued treatment durability. As of January 2025, both these patients are receiving treatment and are continuing to do well. The first patient is an elderly female who had received 16 cycles of treatment over 21 months when first reported on. She continues on study having received 20 cycles over 26 months and she remains in complete remission. The second patient is an elderly male who had received 12 cycles of treatment over 14 months when first reported on. He continues on study having received 16 cycles over 20 months and remains in complete remission. Both patients are being treated with the triple combination of prexigebersen, decitabine and venetoclax.

On February 13, 2025 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultrarare genetic diseases, reported its financial results for the quarter and full year ended December 31, 2024 and shared financial guidance for 2025 (Press release, Ultragenyx Pharmaceutical, FEB 13, 2025, View Source [SID1234650260]).

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"We have created a next-generation rare disease company on a pathway to profitability with meaningful revenue growth from multiple global products and a series of potential new drug approvals," said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. "The major regulatory and clinical catalysts ahead of us this year are the pending PDUFA decision for our gene therapy to treat Sanfilippo syndrome, submission of our second gene therapy biologics license application in Glycogen Storage Disease Type Ia, readout of our pivotal Phase 3 results in osteogenesis imperfecta, and completion of enrollment in our Phase 3 trial in Angelman syndrome."

Fourth Quarter and Full Year 2024 Selected Financial Data Tables and Financial Results

Revenues (dollars in thousands), (unaudited)
Three Months Ended December 31, Year Ended December 31,
2024 2023 2024 2023
Crysvita
Product sales $ 22,415 $ 18,379 $ 134,709 $ 75,697
Revenue in Profit-Share Territory 85,534 70,124 248,966 231,574
Royalty revenue in European Territory 7,473 5,612 25,849 20,783
Total Crysvita Revenue 115,422 94,115 409,524 328,054
Dojolvi 31,103 23,286 88,194 70,633
Evkeeza 10,374 2,102 32,162 3,642
Mepsevii 7,978 7,889 30,350 30,441
Other — — — 1,479
Total revenues $ 164,877 $ 127,392 $ 560,230 $ 434,249

Total Revenues
Ultragenyx reported $165 million in total revenue for the fourth quarter of 2024, which represents 29% growth compared to the same period in 2023. Fourth quarter 2024 Crysvita revenue was $115 million, which represents 23% growth compared to the same period in 2023. This includes product sales of $22 million from Latin America and Turkey, which represents 22% growth compared to the same period in 2023. Dojolvi revenue in the fourth quarter 2024 was $31 million, which represents 34% growth compared to the same period in 2023. Evkeeza revenue in the fourth quarter 2024 was $10 million.

Total revenue for the year ended December 31, 2024 was $560 million, which represents 29% growth compared to the prior year. Full year 2024 Crysvita revenue was $410 million, which represents 25% growth compared to the prior year. This includes product sales of $135 million from Latin America and Turkey, which represents 78% growth compared to the prior year. Dojolvi revenue in 2024 was $88 million, which represents 25% growth compared to the prior year. Evkeeza revenue in 2024 was $32 million, as demand continues to build following launches in the company’s territories outside of the United States.

Selected Financial Data (dollars in thousands, except per share amounts), (unaudited)
Three Months Ended December 31, Year Ended December 31,
2024 2023 2024 2023
Total revenues $ 164,877 $ 127,392 $ 560,230 $ 434,249
Operating expenses:
Cost of sales 16,894 12,051 76,728 45,209
Research and development 187,766 160,557 697,865 648,449
Selling, general and administrative 82,495 76,833 321,610 309,799
Total operating expenses 287,155 249,441 1,096,203 1,003,457
Net loss $ (133,385 ) $ (123,190 ) $ (569,183 ) $ (606,639 )
Net loss per share, basic and diluted $ (1.39 ) $ (1.52 ) $ (6.29 ) $ (8.25 )

Operating Expenses
Total operating expenses for the fourth quarter of 2024 were $287 million, including non-cash stock-based compensation of $40 million. Total operating expenses for the year ended December 31, 2024 were $1,096 million, including $158 million of non-cash stock-based compensation.

Net Loss
For the fourth quarter of 2024, Ultragenyx reported net loss of $133 million, or $1.39 per share basic and diluted, compared with a net loss for the fourth quarter of 2023 of $123 million, or $1.52 per share basic and diluted. For the year ended December 31, 2024, Ultragenyx reported net loss of $569 million, or $6.29 per share basic and diluted, compared with a net loss the prior year of $607 million, or $8.25 per share, basic and diluted.

Cash Balance and Net Cash Used in Operations
Cash, cash equivalents, and marketable debt securities were $745 million as of December 31, 2024. Net cash used in operations for the year ended December 31, 2024 was $414 million.

2025 Financial Guidance
Revenues are expected to grow approximately 14-20% compared to 2024. The company will continue to prioritize expense management, focusing its investments on the execution of multiple upcoming commercial launches and advancing multiple Phase 3 programs. Together, this is expected to lead to a reduction in 2025 net cash used in operations compared to 2024.

For the full year 2025:

Total revenue to be in the range of $640 million to $670 million
Crysvita revenue to be in the range of $460 million to $480 million
Dojolvi revenue to be in the range of $90 million to $100 million
Recent Updates and Clinical Milestones

UX143 (setrusumab) monoclonal antibody for osteogenesis imperfecta (OI): Phase 3 Orbit study progressing to second interim analysis (IA2) expected in mid-2025

Patients continue dosing in the ongoing Phase 3 Orbit and Cosmic clinical trials, which evaluate setrusumab in pediatric and young adult patients with OI. The randomized, placebo-controlled Phase 3 portion of the Orbit study is progressing towards the second interim analysis in mid-2025 or a final analysis in the fourth quarter 2025. Conduct of the study is going well and patient safety in the Phase 3 is consistent with the Phase 2. Patients in the Cosmic study also are continuing to be treated with either setrusumab or intravenous bisphosphonates (IV-BP) therapy and will be evaluated in parallel with the Orbit interim and final analyses.

GTX-102 an antisense oligonucleotide for Angelman syndrome: Phase 3 study enrolling; expect enrollment completion in second half of 2025

Enrollment in the global Phase 3 Aspire study began in December 2024 and is expected to enroll approximately 120 children ages four to 17 with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. Participants will be randomized 1:1 to receive GTX-102 by intrathecal injection via lumbar puncture or to the sham comparator group during the 48-week primary efficacy analysis period. The primary endpoint will be improvement in cognition assessed by Bayley-4 cognitive raw score, and the key secondary endpoint (with a 10% allocation of alpha) will be the Multi-domain Responder Index (MDRI) across the five domains of cognition, receptive communication, behavior, gross motor function, and sleep. Enrollment in the Phase 3 Aspire study is expected to complete in the second half of 2025.

The Phase 2/3 Aurora study, which will evaluate GTX-102 in other Angelman syndrome genotypes and ages, is expected to initiate in 2025.

UX111 AAV gene therapy for Sanfilippo syndrome type A (MPS IIIA): Biologics license application (BLA) submitted; expect Prescription Drug User Fee Act (PDUFA) decision on the application and potential launch in second half of 2025

In December 2024, Ultragenyx submitted a BLA to the U.S. Food and Drug Administration for UX111 supported by the available data, including from the ongoing pivotal Transpher A study. New clinical data were recently presented at WORLDSymposium 2025, that demonstrated treatment with UX111 led to a statistically significant improvement in the Bayley-III raw scores for the subdomains of cognition, receptive communication and expressive communication in patients with MPS IIIA compared to natural history data from untreated patients. These clinical endpoints were correlated with substantial and sustained reduction in levels of heparan sulfate in cerebrospinal fluid. A PDUFA decision and potential launch are expected in the second half of 2025.

DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): BLA filing expected in mid-2025

Ultragenyx previously announced positive topline results from the Phase 3 GlucoGene study for the treatment of patients aged eight years and older. The study achieved its primary endpoint, demonstrating that treatment with DTX401 resulted in a statistically significant and clinically meaningful reduction in daily cornstarch intake compared with placebo at Week 48.

After the 48-week primary efficacy analysis period, crossover patients (previously treated with placebo) were eligible to receive DTX401. These patients were able to titrate cornstarch much more rapidly once they were confirmed to have been treated and had timely direct access to their glucose levels. Patients from the original DTX401 treatment arm who have reached 78 weeks also continued to reduce their daily cornstarch intake, while maintaining glycemic control. DTX401 has demonstrated a consistent and acceptable safety profile with no new safety concerns identified as of the data cut-off.

These results have been discussed with regulatory authorities in a pre-BLA meeting and will be included as part of a BLA submission in mid-2025.

DTX301 AAV gene therapy for Ornithine Transcarbamylase (OTC) Deficiency: Enrollment in Phase 3 study complete

Enrollment in the Phase 3 Enh3ance study has been completed with a total of 37 patients. The pivotal study enrolled participants 12 years of age and older, randomized 1:1 to DTX301 or placebo. The primary endpoints are response as measured by change in 24-hour ammonia levels and removal of ammonia-scavenger medications and protein-restricted diet. Based on the recently amended protocol, the change in 24-hour ammonia levels will be measured through Week 36 after which the study would unblind and patients will be followed for a total of up to 64 weeks to determine the complete responders able to remove safely both ammonia-scavenger medications and protein-restricted diet control.

UX701 AAV gene therapy for Wilson Disease: Phase 1/2/3 study ongoing; expect Cohort 4 enrollment completion in second half of 2025

In Stage 1 of the Phase 1/2/3 Cyprus2+ study, 15 patients across three sequential dose cohorts were enrolled and demonstrated clinical activity as well as improvements in copper metabolism. Multiple responders completely tapered off their standard-of-care treatment with responses seen in all three dose cohorts.

The company expects to enroll a fourth cohort in Stage 1 at a moderately increased dose and with an optimized immunomodulation regimen to enhance the efficiency and efficacy of the gene therapy, with the objective of having the majority of patients come off standard-of-care treatment before selecting a dose for the randomized placebo-controlled stage of the study. Enrollment in Cohort 4 is expected to complete in the second half of 2025.

Conference Call and Webcast Information

Ultragenyx will host a conference call today, Thursday, February 13, 2025, at 2 p.m. PT/5 p.m. ET to discuss the fourth quarter and full year 2024 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at View Source The replay of the call will be available for three months.

On February 13, 2025 Bio-Path Holdings, Inc., (NASDAQ:BPTH), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer and obesity drugs, reported the receipt of newly issued patents in the United States and New Zealand, and updated investors on the extent of its global intellectual property portfolio (Press release, Bio-Path Holdings, FEB 13, 2025, View Source [SID1234650244]).

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Bio-Path received Notice of Allowance from the United States Patent and Trademark Office for U.S. Patent No. 17/339,366 titled, "P-ethoxy nucleic acids for STAT3 inhibition." The New Zealand Intellectual Property Office has granted Patent No. 741793 titled, "P-ethoxy nucleic acids for liposomal formulation." These new patents build on earlier patents granted that protect the platform technology for DNAbilize, the Company’s novel RNAi nanoparticle drugs.

"We are proud of our growing global intellectual property portfolio as it safeguards our technology, serves as a deterrent to would-be competitors and creates value around our core competencies," said Peter Nielsen, Chief Executive Officer of Bio-Path. "These efforts are designed to protect our investments and advance our clinical programs to bring new medicines to patients suffering with obesity and cancer. Importantly, our newly issued U.S. patent provides additional intellectual property protection around our STAT3 program, where we intend to advance into non-small cell lung cancer."

Bio-Path continues to expand its intellectual property portfolio by filing patent applications that are applicable to its technology and business strategy. Bio-Path’s patent portfolio currently includes seven issued patents in the U.S. and 61 issued patents in foreign jurisdictions, providing protection in 26 countries. The Company has three additional pending patent applications in the U.S. and five additional allowed patent applications in foreign jurisdictions.

On February 13, 2025 Oncotelic Therapeutics, Inc (OTCQB:OTLC). Oncotelic Therapeutics, a leader in RNA-based therapeutics, reported that Vuong Trieu, Ph.D., Chairman & CEO, will be delivering a featured presentation at the SWCR 2025 Conference on March 24th (Press release, Oncotelic, FEB 13, 2025, View Source [SID1234650261]). His talk will highlight the central role of Transforming Growth Factor Beta 2 (TGFB2) in the convergence of disease pathways spanning cancer, lupus, and aging, as well as its potential as a therapeutic target in immuno-oncology.

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Dr. Trieu’s presentation, titled "Transforming Growth Factor Beta 2 in Aging, Cancer, Lupus, and Immuno-Oncology: A Convergence of Disease Pathways and Therapeutic Potential," will delve into the immunosuppressive mechanisms of TGFB2 and its profound impact on solid tumors, autoimmune disorders, and age-related diseases. His research underscores how high TGFB2 expression fosters tumor-associated macrophage infiltration, disrupts antigen presentation, and drives resistance to immunotherapy-ultimately contributing to poor patient outcomes.

A key focus of the presentation will be the clinical development of OT-101, an antisense therapeutic targeting TGFB2, which is currently in Phase 3 clinical trials (STOP-PC study) for pancreatic ductal adenocarcinoma (PDAC). The talk will explore how TGFB2 inhibition-alone or in combination with immune checkpoint inhibitors or interferon-based strategies-may reshape the tumor microenvironment, boost immune response, and enhance therapeutic efficacy.

Dr. Vuong Trieu’s Vision for TGFB2 as a Therapeutic Target

"TGFB2 has emerged as a master regulator of immune suppression, not just in cancer but across multiple chronic diseases," said Dr. Trieu. "Our work on OT-101 aims to neutralize TGFB2-driven resistance, unlocking the full potential of immunotherapy and improving outcomes for patients with pancreatic cancer, gliomas, and beyond."

On February 13, 2025 (the "Closing Date"), Sarepta Therapeutics, Inc. (the "Company") and Sarepta Therapeutics Investments, Inc., a wholly owned subsidiary of the Company (together with the Company, the "Obligors") reported to have entered into a credit agreement (the "Credit Agreement") with JPMorgan Chase Bank, N.A., as administrative agent (in such capacity, the "Administrative Agent") and as collateral agent (in such capacity, the "Collateral Agent") and the lenders party thereto (Filing, 8-K, Sarepta Therapeutics, FEB 13, 2025, View Source [SID1234650287]). The Credit Agreement provides for a five-year, $600 million senior secured revolving credit facility (the "Revolving Credit Facility").

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Interest rates under the Revolving Credit Facility are variable and equal to the Secured Overnight Financing Rate plus a credit spread adjustment of 0.10% per annum ("Adjusted SOFR"), plus a margin of 1.125% to 1.75% per annum based on the Company’s total gross leverage ratio, or, at the Company’s option, at a base reference rate equal to the highest of (a) the federal funds rate plus 0.50%, (b) the rate of interest last quoted by the Administrative Agent as its "base rate" and (c) the one-month Adjusted SOFR rate plus 1.00%, plus a margin of 0.125% to 0.75% per annum based on the Company’s total gross leverage ratio.

The Company will pay customary agency fees and a commitment fee based on the daily unused portion of the Revolving Credit Facility at a rate of 0.20% to 0.35% per annum based on the Borrower’s total gross leverage ratio. The Revolving Credit Facility is not subject to amortization and will mature on the fifth anniversary of the Closing Date.

On the Closing Date, each of the Obligors and the Collateral Agent entered into a pledge and security agreement, pursuant to which the Obligors granted a security interest in substantially all of their respective assets, in each case, subject to customary exceptions and exclusions.

The Credit Agreement contains customary representations and warranties, affirmative covenants, negative covenants and events of default. The Credit Agreement also contains financial covenants that are tested on the last day of each of the Company’s fiscal quarters. These financial covenants include a (x) maximum secured net leverage ratio of 3.5:1.0, subject to a 4.0:1.0 covenant holiday following certain permitted acquisitions or permitted collaborations, and (y) minimum consolidated interest coverage ratio of 2.5:1.0.

The foregoing description of the Credit Agreement does not purport to be complete and is subject to, and qualified in its entirety by reference to, the full text of the Credit Agreement, attached hereto as Exhibit 10.1 and incorporated herein by reference.