Entry into a Material Definitive Agreement

On September 29, 2025, ARS Pharmaceuticals, Inc. (the "Company") and certain direct and indirect subsidiaries of the Company who may become a party thereto from time to time, as guarantors (the "Guarantors"), and ARS Pharmaceuticals Operations, Inc., a wholly owned subsidiary of the Company, as the borrower (the "Borrower" and, collectively with the Guarantors, the "Credit Parties"), reported to have entered into a credit agreement (the "Credit Agreement") with RA Capital Agency Services, LLC (as the "Administrative Agent" and as the "Collateral Agent"), and affiliates of OMERS Administration Corporation and RA Capital Management, L.P., as lenders, and such other lenders from time to time party thereto (the "Lenders"), providing for up to $250.0 million of term loans from the Lenders to the Borrower (the "Term Loans") (Filing, ARS Pharmaceuticals, SEP 29, 2025, View Source [SID1234656313]). The proceeds of the Term Loans will be used to (i) fund research, development and other product development and commercialization activities of the Company’s products and (ii) for other general corporate purposes.

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Pursuant to the terms of the Credit Agreement, the Term Loans may be advanced in four tranches. The first tranche (the "Term A Loan") was advanced in the principal amount of $100.0 million on September 29, 2025 ("Closing Date"). The second tranche (the "Term B Loan") in a principal amount of $25.0 million may be advanced at the Borrower’s election during the period commencing on the six-month anniversary of the Closing Date and ending no later than the one-year anniversary of the Closing Date, subject to customary conditions. The third tranche (the "Term C Loan") in a principal amount of $25.0 million may be advanced at the Borrower’s election during the period commencing on and including the Closing Date and ending no later than the two-year anniversary of the Closing Date, subject to achieving trailing 12-month ("TTM") net revenues for neffy of at least $100.0 million and customary conditions. The fourth tranche (the "Term D Loan") of up to $100.0 million is uncommitted and may be advanced at the Borrower’s election, subject to the consent of all of the Lenders who agree to provide the Term D Loan and customary conditions. The Term Loans will mature on the five-year anniversary of the Closing Date ("Maturity Date"). In connection with entering into the Credit Agreement and drawing the Term A Loan, the Credit Parties entered into a security agreement and pledge agreement and delivered other customary deliverables.

The Term Loans will initially bear interest at a per annum rate of 5.50% plus the greater of (i) three-month forward-looking term SOFR or (ii) 3.00%, which interest rate may be reduced by 25 to 50 basis points based on achieving certain TTM net revenues milestones. At Borrower’s election and subject to certain conditions, 100% of accrued interest in the first two years and 50% of accrued interest in the last three years may be paid-in-kind, in which case the applicable interest rate for the Term Loans shall increase by 1.00% per annum for the portion of such Term Loans that is paid-in-kind. The Borrower will pay certain fees with respect to the Term Loans, including an upfront fee, an administration fee, a repayment premium and an exit fee, as well as certain other fees and expenses of the Administrative Agent and the Lenders.

The obligations of the Borrower under the Credit Agreement are guaranteed on a full and unconditional basis by the Company and the Guarantors and are secured by substantially all of the respective Credit Parties’ tangible and intangible assets and property, including intellectual property, subject to certain exceptions.

The Credit Agreement includes representations and warranties, affirmative covenants (including reporting obligations), negative covenants (including restrictions on making certain investments, incurring additional indebtedness, granting liens, disposing of assets, making certain payments (e.g., dividends), prepayments of other indebtedness, and failing to maintain a minimum liquidity threshold) and events of default that are usual and customary for facilities of this type, in each case, subject to certain permitted exceptions as set forth therein.

The Administrative Agent and Collateral Agent, as well as a Lender, are affiliates of RA Capital Management, L.P. ("RA Capital"). The general partner of RA Capital is RA Capital Management GP, LLC, of which Peter Kolchinsky, Ph.D. and Rajeev Shah are controlling persons. RA Capital Healthcare Fund, L.P. and RA Capital Nexus Fund II, L.P. collectively hold in excess of 10% of the Company’s outstanding common stock and are currently the Company’s largest stockholder. RA Capital serves as the investment adviser for each of RA Capital Healthcare Fund, L.P. and RA Capital Nexus Fund II, L.P. Dr. Kolchinsky serves as a member of the Company’s board of directors.

The foregoing summary of the Credit Agreement is not complete and is qualified in its entirety by reference to the Credit Agreement, a copy of which is filed as Exhibit 10.1 to this report.

TAE Life Sciences Novel Boronated Drugs for BNCT in Combination with Immune Checkpoint Inhibitors Demonstrate Superior Tumor Growth Inhibition in Preclinical in vivo Models

On September 29, 2025 TAE Life Sciences (TLS) reported preclinical results from its collaboration with Kyoto University, demonstrating that its next-generation boron drugs, when combined with immune checkpoint inhibitors, significantly inhibited tumor growth in certain conditions compared with either immunotherapy alone or BNCT alone (Press release, TAE Life Sciences, SEP 29, 2025, View Source [SID1234656331]). Based on the ongoing success of this collaboration and the exciting data being generated, TLS and Kyoto University have extended their BNCT research partnership through December 2026.

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TLS’s findings are consistent with recent third-party publications highlighting the unique synergy between BNCT and checkpoint inhibitors. Both independent 2024 studies from Japan reported that combining BNCT with PD-1/PD-L1 blockade enhanced tumor control and survival, reinforcing TLS’s own observations of synergistic immune activation. This alignment underscores the translational potential of TLS’s BNCT-immunotherapy strategy.

"These preclinical results with TLS proprietary boronated compounds confirm the potential to not only deliver targeted BNCT but also amplify the effects of immunotherapy," said Rob Hill, CEO of TAE Life Sciences. "This in turn expands our clinical opportunity and strengthens our position in both oncology and the fast-growing immunotherapy markets."

"Our partnership with Kyoto University has been critical in driving novel drug development for BNCT," added Kendall Morrison, Chief Scientific Officer at TLS. "By extending this partnership through 2026, we ensure continuity in preclinical testing, combination optimization, and translational research that supports our IND-enabling path."

Strategic outlook

These results reinforce the potential for TLS’s novel boronated drugs to transform BNCT from a targeted radiation therapy into a powerful immuno-oncology strategy. By combining the precision of BNCT with the systemic effects of checkpoint inhibition, these drugs may help overcome resistance, broaden patient benefit, and establish a new standard for difficult-to-treat cancers. The extension of TLS’s partnership with Kyoto University provides a strong foundation to advance this program toward IND-enabling studies, first-in-human trials and upcoming scientific milestones.

Enhertu demonstrated highly statistically significant and clinically meaningful improvement in invasive disease-free survival vs. T-DM1 in DESTINY-Breast05 Phase III trial in patients with high-risk early breast cancer following neoadjuvant therapy

On September 29, 2025 Astrazeneca reported positive high-level results from a planned interim analysis of the DESTINY-Breast05 Phase III trial showed Enhertu (trastuzumab deruxtecan) demonstrated a highly statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS) versus trastuzumab emtansine (T-DM1) in patients with HER2-positive early breast cancer with residual invasive disease in the breast or axillary lymph nodes after neoadjuvant treatment and a high risk of disease recurrence (Press release, AstraZeneca, SEP 29, 2025, View Source [SID1234656314]). This is the second positive Phase III trial of Enhertu in the HER2-positive early breast cancer setting following positive results from the DESTINY-Breast11 Phase III neoadjuvant trial earlier this year.

Overall survival (OS) was not mature at the time of this planned interim analysis and will be assessed at a subsequent analysis.

Currently, approximately half of patients with HER2-positive early breast cancer have residual disease following neoadjuvant treatment, putting them at an increased risk of disease recurrence.1-7 Despite receiving additional treatment in the post-neoadjuvant setting with current standards of care, some patients still ultimately experience tumour progression to metastatic disease.8-10 New treatment options are needed in the early breast cancer setting to help reduce the likelihood of disease progression and improve long-term outcomes for more patients.10-11

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "This landmark trial is the first to directly compare Enhertu and T-DM1 in early breast cancer, and the results clearly show that Enhertu delivers superior outcomes, indicating that it may be a better option for patients with high-risk HER2-positive disease in the post-neoadjuvant setting. These results from DESTINY-Breast05, coupled with DESTINY-Breast11, underscore our commitment to moving Enhertu into early-stage HER2-positive breast cancer where patients can achieve sustained long-term outcomes, increasing the opportunity for cure."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "In patients with early breast cancer with residual disease following neoadjuvant treatment, it is critical to optimise treatment as this represents the last opportunity to prevent progression to metastatic disease. The results of DESTINY-Breast05 demonstrate that treatment with Enhertu following surgery increases the length of time patients are able to live free of invasive disease compared to the existing standard of care, potentially offering patients with HER2-positive early breast cancer a new treatment approach in this curative-intent setting."

The safety profile of Enhertu observed in DESTINY-Breast05 was consistent with its known profile with no new safety concerns identified.

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Data from DESTINY-Breast05 (Abstract #LBA1) and DESTINY-Breast11 (Abstract #291O) will be presented during Presidential Symposium 1 on 18 October at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025. The DESTINY-Breast05 data will also be shared with global regulatory authorities.

DESTINY-Breast05 was conducted in collaboration with the National Surgical Adjuvant Breast and Bowel Project Foundation (NSABP), the German Breast Group (GBG), Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-B) and SOLTI Breast Cancer Research Group.

Notes

HER2-positive early breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.12 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.12

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast cancer.13 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.14 Approximately one in five cases of breast cancer are considered HER2-positive.15

Currently, approximately half of patients with HER2-positive early breast cancer have residual disease following neoadjuvant treatment, putting them at an increased risk of disease recurrence.1-7 Despite receiving additional treatment in the post-neoadjuvant setting, some patients still ultimately experience tumour progression to metastatic disease.8-10 Once patients are diagnosed with metastatic disease, the five-year survival rate drops from nearly 90 percent to approximately 30 percent.16 New treatment options are needed in the early breast cancer setting to help reduce the likelihood of disease progression in order to improve long-term outcomes for more patients.10-11

DESTINY-Breast05
DESTINY-Breast05 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus trastuzumab ematansine (T-DM1) in patients with HER2-positive primary breast cancer that are at high risk of recurrence and have residual invasive disease in breast or axillary lymph nodes following neoadjuvant therapy. High risk of recurrence was defined as presentation with inoperable cancer (prior to neoadjuvant therapy) or pathologically positive axillary lymph nodes following neoadjuvant therapy.

The primary endpoint of DESTINY-Breast05 is investigator-assessed IDFS. IDFS is defined as the time from randomisation until first occurrence of invasive breast cancer recurrence, distant recurrence, or death from any cause. The key secondary endpoint is investigator-assessed disease-free survival. Other secondary endpoints include OS, distant recurrence-free interval, brain metastases-free interval and safety.

DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, Oceania, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu (5.4mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC 3+ or in-situ hybridisation [ISH]+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4mg/kg) is approved in more than 45 countries/regions for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

Enhertu (5.4mg/kg) is approved in more than 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in more than 70 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may by contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (5.4mg/kg) is approved in more than 10 countries/regions for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu development programme
A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. Trials in combination with other anti-cancer treatments, such as immunotherapy, also are underway.

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Aarvik Therapeutics Announces Successful Series Seed 2 Financing Round

On September 29, 2025 Aarvik Therapeutics, an innovative, ADC-focused biotechnology company dedicated to engineering precision medicines for cancer therapy, reported that it has successfully closed a Series Seed 2 financing round (Press release, Aarvik Therapeutics, SEP 29, 2025, View Source [SID1234656332]).

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Following its launch in 2021, Aarvik closed an initial Series Seed financing round and signed a research collaboration agreement. Aarvik established laboratories in Hayward and developed its proprietary MUTTA (MUlti-epitope Targeting Tetravalent Antibody; pronounced MOO-TA) platform with a focus on developing next generation antibody drug conjugates (ADCs) that can expand the success of ADCs beyond a limited number of targets. Aarvik’s comprehensive approach facilitates the lowering of the minimum effective dose (MED) while maintaining or improving the maximum tolerated dose (MTD), thereby significantly improving the therapeutic window. In August 2024, the option was exercised to exclusively license the research collaboration program.

Aarvik’s new round of funding further validates the substantial progress made by Aarvik on the MUTTA platform. The funding comes from a diverse set of investors that includes original Series Seed investors as well as a new group of pharma and tech professionals, and contract research and contract development and manufacturing organizations. This funding will allow Aarvik to reach targeted research milestones and further advance its pipeline of ADC assets.

"We are delighted to see Aarvik reach this new milestone," said Ram K. Reddy, serial entrepreneur, venture partner and Independent Board Member of Aarvik Therapeutics. "The support from new as well as existing investors is a reflection of the progress achieved by Aarvik and the potential of Aarvik’s pipeline."

"Aarvik continues to demonstrate that it can combine its deep ADC drug development expertise with its next-generation MUTTA platform to enable powerful oncology therapies," said Jagath Reddy Junutula, PhD, Co-founder, President and CEO of Aarvik Therapeutics. "Aarvik relentlessly pursues novel therapies for hard-to-treat cancer indications through research and innovation."

Avenzo Therapeutics Initiates Phase 1/2 Clinical Study of AVZO-103, a Potential Best-in-Class Nectin4/TROP2 Bispecific Antibody-Drug Conjugate

On September 29, 2025 Avenzo Therapeutics, Inc. ("Avenzo"), a clinical-stage biotechnology company developing next-generation oncology therapies, reported initiation of a Phase 1/2 clinical study of its potential best-in-class Nectin4/TROP2 bispecific antibody-drug conjugate, AVZO-103, in patients with advanced solid tumors (Press release, Avenzo Therapeutics, SEP 29, 2025, View Source [SID1234656315]).

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"Nectin4 and TROP2 are highly co-expressed in multiple solid tumors, including urothelial cancer, and contribute to tumor growth and progression," said Benjamin Garmezy, M.D., Associate Director of Genitourinary Research, Sarah Cannon Research Institute. "By targeting both Nectin4 and TROP2, AVZO-103 has the potential to overcome tumor heterogeneity, while also delivering a potent cytotoxic payload that could help overcome resistance to prior therapies."

The Phase 1/2 first-in-human, open-label clinical study is designed to assess the safety, tolerability, and preliminary clinical activity of AVZO-103 as a single agent and in combination therapy in patients with advanced solid tumors.

"The initiation of this study marks our fourth clinical stage program at Avenzo, and reflects our commitment to advancing innovative therapies for patients with cancer," said Mohammad Hirmand, M.D., Co-founder and Chief Medical Officer of Avenzo Therapeutics. "We believe AVZO-103 potentially offers a differentiated approach to treating multiple solid tumors, especially urothelial cancer, and look forward to exploring its potential in the Phase 1/2 study."