As filed with the Securities and Exchange Commission on December 16, 2025 Registration No. 333-291852 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 Amendment No. 1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Edison Oncology Holding Corp. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) Nevada 2836 83-1614120 (Primary Standard Industrial Classification Code Number) 3475 Edison Way, Suite R Menl ...

Core Insights - Clene Inc. has completed FDA-recommended biomarker analyses for CNM-Au8 in ALS patients, showing significant reductions in neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), indicating a potential link between biomarker decline and improved survival [1][2][3] Biomarker Analyses - The FDA recommended three specific analyses to strengthen the evidence for CNM-Au8's effect on NfL and its relationship to clinical benefit, including evaluations in the NIH-sponsored Expanded Access Program (NIH-EAP) [3] - Statistically significant reductions in NfL and GFAP were observed in participants treated with CNM-Au8, with improvements strongly associated with longer survival [3][4] - The analyses confirmed the robustness of findings across various pre-specified supportive analyses, with significant effects noted in specific participant subgroups [4][5] Survival Benefit - Updated survival analyses indicate that CNM-Au8 treatment demonstrated a statistically significant survival benefit compared to controls, with a 73% reduction in the risk of death in the full analysis set and a 77% reduction in a risk-balanced population [6][7] - Even among a small cohort of participants who switched from placebo to CNM-Au8, a significant survival benefit was observed, with an average increase of 30.7 days in survival [7] Safety Profile - CNM-Au8 has shown a strong safety profile across over 1,000 patient years of exposure, with no serious adverse events related to the treatment identified [8] Regulatory Pathway - Clene has requested a Type C meeting with the FDA to present the completed analyses and plans to submit a New Drug Application (NDA) under the accelerated approval pathway in early 2026 [11][12]

Core Viewpoint - PDS Biotechnology Corporation is seeking an accelerated approval pathway for its investigational treatment PDS0101 in HPV16-positive recurrent and/or metastatic Head and Neck Cancer, following positive results from the VERSATILE-002 trial [2][3] Group 1: FDA Meeting and Approval Pathway - The FDA has accepted PDS Biotechnology's request for a Type C Meeting to discuss the proposed accelerated approval pathway for PDS0101 [1] - The proposed amendment to the VERSATILE-003 Phase 3 trial aims to change the progression-free survival (PFS) endpoint to a surrogate primary endpoint, allowing for earlier evaluation with significant statistical power [2] - Median overall survival (mOS) will remain the primary endpoint for full approval as originally recommended by the FDA [2] Group 2: Clinical Trial Insights - The VERSATILE-002 trial demonstrated promising median overall survival and durable progression-free survival in patients with CPS ≥ 1 [2] - The company believes that the positive PFS data from VERSATILE-002 presents an opportunity to shorten the duration to a primary endpoint and potentially accelerate regulatory submission [3] Group 3: Company Overview - PDS Biotechnology is a late-stage immunotherapy company focused on transforming immune system responses to cancer [4] - The lead investigational treatment, PDS0101 (Versamune HPV), is being developed in combination with a standard-of-care immune checkpoint inhibitor and in a triple combination including PDS01ADC, an IL-12 fused antibody drug conjugate [4]

Financial Data and Key Metrics Changes - For Q3 2025, the company reported a loss from operations of $4 million, compared to a loss of $3 million in Q3 2024, primarily due to increased R&D expenses of $800,000 and additional administrative expenses of $400,000 [28][29] - The company generated revenue for the first time, approximately $240,000, reflecting only 22 days of operations from a single clinic [29][30] - As of September 30, 2025, the company had approximately $7.1 million in cash and cash equivalents, with total cash potentially reaching $10.3 million [29] Business Line Data and Key Metrics Changes - The company has advanced its drug approval applications for Ketaphree, NRx 100, and NRx 101, and has expanded its NRx 101 pipeline [3][4] - Hope Therapeutics, a subsidiary, initiated revenue generation with the acquisition of Durra Medical, and plans to expand from two clinics to six or more by year-end [12][26] Market Data and Key Metrics Changes - The market for ketamine is projected at approximately $750 million, with the potential for significant growth through the introduction of preservative-free formulations [21][22] - The estimated market for NRx 101, targeting suicidal bipolar depression, exceeds $1 billion [26] Company Strategy and Development Direction - The company aims to transform the treatment of severe depression and PTSD through innovative therapies combining D-cycloserine and TMS [4][10] - The strategy includes expanding clinic operations and integrating new treatment protocols to enhance patient outcomes and revenue growth [12][30] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the future, anticipating significant revenue growth as more clinics are integrated and additional acquisitions are pursued [12][30] - The leadership highlighted the importance of addressing the national crisis of suicide and the potential for their therapies to meet unmet medical needs [28][30] Other Important Information - The company holds rights to over 70 patents related to the use of D-cycloserine in treating various brain disorders [6] - The FDA has granted breakthrough therapy designation for NRx 101, and the company is pursuing accelerated approval pathways for its drug applications [22][36] Q&A Session Summary Question: Can you clarify the unique benefits of DCS compared to ketamine in treatment? - Management explained that DCS acts as a mixed agonist-antagonist and enhances neuroplasticity, which may improve the effectiveness of TMS [32][34] Question: What is the anticipated timeline for FDA feedback on accelerated approval? - The company expects to hear about the Commissioner's National Priority Voucher (CMPV) this year, which could impact the PDUFA timeline [36][37] Question: How will the company ensure adequate supply if the FDA bans preservative-containing formulations? - The company has a manufacturing process that allows for high production capacity, potentially supplying all required ketamine in the U.S. [38] Question: What is the commercialization strategy for NRx 100 and NRx 101? - NRx 100 will likely require a medical science liaison approach, while NRx 101 may necessitate a sales force due to its specific target market [40][41]

Core Insights - Denali Therapeutics Inc. (DNLI) announced that the FDA has extended the review timeline for its Biologics License Application (BLA) for tividenofusp alfa, a treatment for mucopolysaccharidosis type II (MPS II) [1][3][7] - The new target date for the BLA review is now April 5, 2026, pushed back from January 5, 2026, due to the submission of updated clinical pharmacology information [3][7] - The extension is classified as a major amendment and is not related to the drug's efficacy, safety, or biomarkers [3][4][7] Company Performance - Denali's stock experienced a decline of 26.5% year to date, contrasting with the industry average gain of 9.2% [2] Drug Development Details - Tividenofusp alfa is designed to deliver the iduronate 2-sulfatase (IDS) enzyme to address symptoms of Hunter syndrome [4][5] - The FDA has previously granted Fast Track and Breakthrough Therapy designations to tividenofusp alfa, and the European Medicines Agency has given it Priority Medicines designation [8] Other Pipeline Candidates - Denali is also developing DNL126 for Sanfilippo syndrome type A (MPS IIIA), with the FDA considering cerebrospinal fluid heparan sulfate as a potential surrogate endpoint for accelerated approval [9] - Another candidate, TAK-594/DNL593, is in collaboration with Takeda for treating frontotemporal dementia (FTD) [10] - Denali and Biogen are jointly evaluating BIIB122/DNL151 for Parkinson's disease, with a global phase IIb study currently ongoing [11][12] Market Position - Denali currently holds a Zacks Rank 3 (Hold), while competitors Amicus Therapeutics and CorMedix have higher rankings of 1 (Strong Buy) and 2 (Buy) respectively [13]

Core Viewpoint - Disc Medicine, Inc. has submitted a New Drug Application (NDA) to the FDA for bitopertin, targeting patients aged 12 and older with erythropoietic protoporphyria (EPP), aiming for accelerated approval due to significant unmet medical needs [1][2][3] Company Overview - Disc Medicine is a clinical-stage biopharmaceutical company focused on developing novel treatments for serious hematologic diseases, with a portfolio targeting heme biosynthesis and iron homeostasis [9] Product Details - Bitopertin is an investigational, orally administered inhibitor of glycine transporter 1 (GlyT1), designed to modulate heme biosynthesis and potentially serve as the first disease-modifying therapy for erythropoietic porphyrias [4][5] - The NDA submission is supported by Phase 2 BEACON and AURORA studies, which showed significant reductions in protoporphyrin IX (PPIX) and improvements in light tolerance and quality of life for EPP patients [2][4] Regulatory Pathway - The NDA includes a request for Priority Review, which could shorten the FDA review period to six months, highlighting the potential for significant improvement in treatment effectiveness [3][7] Disease Context - Erythropoietic protoporphyria (EPP) is a rare and debilitating disease caused by mutations affecting heme biosynthesis, leading to severe reactions to sunlight and potential liver complications [6][8]

Core Viewpoint - OS Therapies is advancing its regulatory submissions for OST-HER2, focusing on obtaining marketing authorizations in the UK and US for the treatment of pulmonary metastatic osteosarcoma, with submissions expected in late 2025 and early 2026 [3][7]. Regulatory Update - The company has updated its regulatory filing sequence to prioritize the UK MHRA conditional Marketing Authorisation Application (MAA) submission, which is expected to be completed in December 2025, followed by the US FDA Biologics Licensing Application (BLA) submission in January 2026 [3][7]. - A conditional MAA Pre-Submission Request has been submitted to the MHRA, and the company anticipates receiving formal acceptance for a rolling review request soon [4]. Clinical Trial Insights - The information in the MHRA conditional MAA submission aligns closely with the planned US FDA BLA submission, with the exception of the acceptable comparator arm for efficacy data [5]. - The company aims to use immune activation biomarker data as a surrogate marker correlated with overall survival to support its Accelerated Approval request [5][7]. Company Background - OS Therapies is a clinical-stage oncology company focused on developing treatments for osteosarcoma and other solid tumors, with OST-HER2 being its lead asset [8]. - OST-HER2 has received several designations from the FDA, including Rare Pediatric Disease Designation and Fast-Track designation, and has shown statistically significant benefits in its Phase 2b clinical trial [8]. Future Developments - The company is also advancing its next-generation Antibody Drug Conjugate (ADC) platform, known as tunable ADC (tADC), which utilizes proprietary technology for enhanced drug delivery [9].

Core Insights - Denali Therapeutics reported a second-quarter 2025 loss of $0.72 per share, which was narrower than the Zacks Consensus Estimate of a loss of $0.74, but wider than the loss of $0.59 in the same quarter last year [1][8] - The company did not generate any collaboration revenues in the reported quarter, missing the Zacks Consensus Estimate of $25 million [2] - Year-to-date, shares of Denali have declined by 31.7%, while the industry has only seen a 0.6% decline [2] Financial Performance - Research and development expenses increased by 12.4% to $102.7 million, primarily due to higher spending on multiple preclinical programs and increased costs for consultants and general facilities [4] - General and administrative expenses rose by 28% to $32.3 million, driven by preparations for the potential launch of tividenofusp alfa [4] - As of June 30, 2025, the company had cash, cash equivalents, and marketable securities totaling approximately $977.4 million [5] Pipeline Developments - The FDA accepted Denali's biologics license application (BLA) for tividenofusp alfa for priority review, with a target action date set for January 5, 2026 [6][8] - The BLA seeks accelerated approval based on data from a phase I/II study in individuals with Hunter syndrome, with previous designations from the FDA including Breakthrough Therapy and Fast Track [7] - Denali is also advancing DNL126 for Sanfilippo syndrome type A, with alignment from the FDA on using cerebrospinal fluid heparan sulfate as a surrogate endpoint for accelerated approval [10] Ongoing Studies - Data from the ongoing phase I/II study of DNL126 shows a significant reduction in cerebrospinal fluid heparan sulfate levels, supporting continued development [11] - Denali is conducting a phase I/II study of DNL593 for frontotemporal dementia, in collaboration with Takeda [12] - The company is also evaluating BIIB122/DNL151 in partnership with Biogen for Parkinson's disease, with a global phase IIb study fully enrolled [13][14] Future Plans - Denali plans to submit regulatory applications for one to two TV-enabled programs each year over the next three years across its various franchises [15] - The most advanced programs include DNL952 for Pompe disease and DNL111 for Parkinson's/Gaucher disease, among others [15] Overall Assessment - Denali's recent pipeline progress is viewed positively, with potential approval of tividenofusp alfa expected to significantly boost the company [16] - The strong cash position is seen as a positive factor for funding ongoing programs [16]

Summary of Laramar Therapeutics Conference Call Company Overview - **Company**: Laramar Therapeutics - **Focus**: Development of nonlobofusp (formerly CTI-16-01) for the treatment of Friedreich's Ataxia (FA), a rare neurodegenerative disease [doc id='13'][doc id='16'] Industry Context - **Disease**: Friedreich's Ataxia (FA) is characterized by low levels of frataxin, leading to severe neurological symptoms and a life expectancy of 30 to 50 years [doc id='15'][doc id='14'] - **Current Treatments**: The FDA approved omevaloxolone in 2023, but it does not affect frataxin levels, highlighting the unmet need for therapies that address the underlying deficiency [doc id='16'] Key Regulatory Updates - **FDA Recommendations**: Laramar received FDA guidance on the safety database for the Biologics License Application (BLA) submission, requiring data from at least 30 participants exposed to the drug for six months and 10 participants for one year [doc id='7'][doc id='8'] - **BLA Submission Timeline**: The company plans to submit the BLA in Q2 2026, with a U.S. launch targeted for early 2027 [doc id='25'][doc id='31'] Clinical Development - **Clinical Trials**: Ongoing studies include a global Phase 3 trial and an open-label extension study to evaluate long-term safety and efficacy [doc id='11'][doc id='12'] - **Patient Population**: The Phase 3 study will include patients aged 2 to 40, with a focus on younger patients [doc id='28'][doc id='29'] - **Efficacy Data**: Initial data from the 25 mg dose showed increases in frataxin levels and early trends towards clinical improvement [doc id='19'][doc id='20'] Safety Profile - **Adverse Events**: Nonlobofusp has been generally well tolerated, with mild injection site reactions being the most common adverse events [doc id='20][doc id='21'] - **Allergic Reactions**: Anaphylaxis has been reported, particularly in patients with prior exposure, leading to the introduction of antihistamine premedication [doc id='21'][doc id='22'] Financial Position - **Cash Balance**: As of March 31, the company reported $158 million in cash, sufficient to support operations through the BLA filing [doc id='61'] - **Funding Strategy**: Laramar is exploring non-dilutive financing options, including royalty financing [doc id='61] Future Plans - **Expansion of Studies**: The company plans to enroll children aged 2 to 11 directly into the open-label study, pending FDA discussions [doc id='26'][doc id='105'] - **Data Reporting**: Upcoming data cuts in September will include safety and pharmacokinetic data from 30 to 40 participants [doc id='26'][doc id='39'] Conclusion - Laramar Therapeutics is making significant progress in the development of nonlobofusp for FA, with clear regulatory guidance from the FDA and a robust clinical program aimed at addressing the unmet needs of patients with this debilitating disease [doc id='30'][doc id='31']

Core Viewpoint - Larimar Therapeutics, Inc. is progressing towards the submission of a Biologics License Application (BLA) for nomlabofusp, a potential treatment for Friedreich's Ataxia, with a planned submission in the second quarter of 2026 following FDA recommendations for safety data inclusion [1][4][9] FDA Recommendations - The FDA has provided clear recommendations for the safety database, requiring at least 30 participants with continuous exposure for 6 months, including a subset of at least 10 participants with 1-year exposure, primarily from the 50 mg dose group [4][5] - The FDA is open to the use of skin frataxin (FXN) concentrations as a reasonably likely surrogate endpoint for the BLA submission, acknowledging the relationship between increased skin FXN and relevant tissues [5][9] Clinical Development Progress - Enrollment in the open label extension (OLE) study is ongoing, with plans to include adolescents and patients who have not previously participated in clinical studies [2][4] - Data from the OLE study, expected in September 2025, will include results from 30-40 participants who received at least one dose of nomlabofusp, focusing on the 50 mg dose [4][9] - Adolescent pharmacokinetic (PK) run-in data is also anticipated in September 2025 from 14 participants, some of whom received a placebo [4][9] Global Phase 3 Study - Activities for the global Phase 3 study are ongoing, with site identification and qualification in the U.S., Europe, U.K., Canada, and Australia [4][9] - The Phase 3 study is intended to serve as a confirmatory study to verify clinical benefit as required by the FDA's accelerated approval pathway [9] Company Overview - Larimar Therapeutics is a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, with nomlabofusp as its lead compound targeting Friedreich's Ataxia [7]