On January 15, 2025 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM" or the "Company") reported key clinical, regulatory and corporate milestones achieved over 2024 and outlined its expected upcoming milestones (Press release, AIM ImmunoTech, JAN 15, 2025, View Source [SID1234649733]).

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"It is clear that 2024 was a foundational year for AIM on the clinical, regulatory and corporate fronts. Without a doubt, our team continued to drive our strategy forward and deliver results. We believe this progress has positioned AIM for an exciting 2025 and the opportunity to drive value for our stockholders," stated Thomas K. Equels, Chief Executive Officer of AIM ImmunoTech. "Looking ahead, we believe we are poised for an exciting 2025 with a number of key milestones expected over the next 18 months across important clinical trials addressing major unmet medical needs. Certain of these trials are being funded in part by major oncology interests such as the National Cancer Institute, AstraZeneca and Merck, which we believe emphasizes their great potential to change lives for the better. Our team is committed to the seamless execution of our clinical development programs and, if successful, we believe each holds the potential to drive significant value in the near and long term."

2024 Clinical Achievement Highlights

Metastatic Pancreatic Ductal Adenocarcinoma Program

Commenced enrollment and dosing in DURIPANC Phase 1b/2 study combining Ampligen with AstraZeneca’s anti-PD-L1 immune checkpoint inhibitor Imfinzi (durvalumab) for the treatment of late-stage pancreatic cancer;
Announced that the first dose level was generally well-tolerated in the DURIPANC Phase 1b/2 study of Ampligen and Imfinzi as a combination therapy for late-stage pancreatic cancer; and
Reported positive preliminary data from Phase 1b/2 study of Ampligen and Imfinzi as a combination therapy for late-stage pancreatic cancer.
Phase 2 Locally Advanced Pancreatic Adenocarcinoma Program

Received authorization from the Erasmus Medical Center Ethics Committee to open a European site for the ongoing Phase 2 study ("AMP-270") of Ampligen as a therapy for locally advanced pancreatic cancer; and
Announced the publication of new positive data analysis from a long-term Early Access Program studying Ampligen for the treatment of advanced pancreatic ductal adenocarcinoma.
The Company sought FDA guidance on expansion of inclusion criteria and treatment arms, and then subsequently amended the study protocol. The study is recruiting patients. These adjustments are also expected to result in substantial reductions in clinical costs.
Phase 2 Recurrent Ovarian Cancer Program

Reported positive top-line, protocol-planned interim report data from the study of Ampligen combined with pembrolizumab for the treatment of recurrent ovarian cancer.
Phase 2 Post-COVID Conditions Program

Reported positive topline results from the Company’s Phase 2 study evaluating the efficacy and safety of Ampligen as a potential therapeutic for people with the post-COVID condition of fatigue ("AMP-518"); and
Reported an analysis of the AMP-518 clinical trial, based upon statistically significant data, which supports the Company’s belief in Ampligen as a potential therapeutic for people with the moderate-to-severe post-COVID-19 condition of fatigue, and that this would be the likely subject population for AIM’s planned follow-up clinical trial.
Grants of Intellectual Property in 2024
Further, the Company was also granted two important patents covering Ampligen for the treatment of:

Endometriosis, a painful chronic condition that affects nearly 10% of women of reproductive age, or approximately 6.5 million women in the United States. This patent was granted in the United States.
The Post-COVID Condition of Fatigue. This method and compositions patent was granted in the Netherlands.
Additionally, AIM successfully completed cGMP manufacturing of 9,042 clinical vials of Ampligen. The Company announced the publication of new pre-clinical data of Ampligen as part of a combinational therapy in the treatment of melanoma.

Expected Upcoming, Value-Driving Milestones

Metastatic Pancreatic Ductal Adenocarcinoma
Phase 1b/2 Combining Anti-PD-L1 Immune Checkpoint Inhibitor Durvalumab with TLR-3 Agonist Ampligen in Patients with Metastatic Pancreatic Ductal Adenocarcinoma for Therapy Efficacy (DURIPANC) (NCT05927142); Funded through collaboration of AstraZeneca and Erasmus Medical Center

Q1 2025: Complete Phase 1b
Early Q2 2025: Launch of Phase 2
Q2/Q3 2026: Last patient enrolled in Phase 2
Locally Advanced Pancreas Cancer (LAPC)
Phase 2 Ampligen Combined with Standard of Care (SOC) versus SOC Alone Following First-Line Therapy in Subjects with LAPC (NCT05494697); AIM funded

Q1 2025: Buffet Cancer Center expected to enroll first subject
H1 2025: first subject dosed
Refractory Melanoma
Phase 2 Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Ampligen, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (NCT04093323); Grant funded by National Cancer Institute

H1 2025: First patient dosed
Stage 4 Triple Negative Breast Cancer
Phase 1/2a Study of Ampligen, Celecoxib and Interferon Alpha 2b with Pembrolizumab for the Treatment of Patients with Metastatic or Unresectable Triple Negative Breast Cancer (NCT05756166); Grant funded by Merck and National Cancer Institute

Q2 2026: Expected completion of enrollment
Advanced Recurrent Ovarian Cancer
Phase 2 Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer (NCT03734692); Grant funded by Merck

H1 2025: Expected last patient dosed and completion of study
Advanced Recurrent Ovarian Cancer
Phase 2 Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines (NCT02432378); Grant funded by the National Cancer Institute

H1 2025: First patient dosed
Post COVID Chronic Fatigue Conditions / Long Covid
Phase 2 Study to Evaluate the Efficacy and Safety of Ampligen in Patients with Post-COVID Conditions (NCT05592418); AIM funded

Q1 2025: Final approved study results to be published on clinicaltrials.gov

On January 14, 2025 Alphamab Oncology (stock code: 9966.HK) reported that the first patient has been successfully dosed in Fudan University Shanghai Cancer Center in the phase I/II clinical study (Study ID: JSKN033-102) of JSKN033, a high-concentration subcutaneous co-formulation consisting of anti-HER2 bispecific antibody-drug conjugate (ADC) and PD-L1 immune checkpoint inhibitor, for the treatment of advanced metastatic malignant tumors.

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JSKN033 is the global first high-concentration subcutaneous co-formulation consisting of ADC and PD-L1 immune checkpoint inhibitor in first-in-human clinical trial, which is independently developed by the Company. By combining immunotherapy and ADC, JSKN033 is anticipated to significantly enhance efficacy. Leveraging the superior solubility and stability of Envafolimab, this formulation makes ADC subcutaneous injectable and leads to improved safety and convenience. The first-in-human phase I/II clinical study of JSKN033 conducted in Australia demonstrated favorable safety profile and encouraging anti-tumor activity.

JSKN033-102 is an open-label, multicenter, Phase Ⅰ/Ⅱ clinical study designed to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics and anti-tumor activity of JSKN033 in Chinese patients with advanced metastatic malignant tumors, and to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D). This study has previously been included in the "Pilot Program for Optimizing the Review and Approval of Clinical Trials for Innovative Drugs".

About JSKN033

JSKN033 is the global first high-concentration subcutaneous co-formulation consisting of ADC (JSKN003) and immune checkpoint inhibitor (Envafolimab), which is independently developed by the Company. JSKN003 is a an anti-HER2 bispecific ADC, comprising of three components: a bispecific antibody targeting two non-overlapping epitopes of HER2 extracellular domains, a cleavable linker, and a topoisomerase I inhibitor. Envafolimab is a Fc fusion protein consisting of humanized anti-PD-L1 single domain antibody and human IgG1 Fc fragment, which has been approved by Chinese authorities as the global-first subcutaneous injection PD-(L)1 inhibitor in November 2021. By combining immunotherapy and ADC, JSKN033 is anticipated to significantly enhance efficacy. Leveraging the superior solubility and stability of Envafolimab, this formulation makes ADC subcutaneous injectable and leads to improved safety and convenience. The phase I/II clinical study of JSKN033 for the treatment of advanced or metastatic solid tumors is currently being conducted in China and Australia.

(Press release, Alphamab, JAN 14, 2025, View Source [SID1234657007])

On January 14, 2025 AimedBio reported it has entered into an exclusive global license agreement with U.S.-based Biohaven for the development and commercialization of AMB302, an FGFR3-targeting ADC.

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– Under the agreement, Biohaven will lead the Phase 1 clinical trial in the United States.

– Financial details, including upfront payments and the total deal size, were not disclosed.

(Press release, AimedBio, JAN 14, 2025, View Source;s_keyword=&s_where=&start=10 [SID1234656918])

On January 14, 2025 Parabilis Medicines (formerly Fog Pharmaceuticals), a clinical-stage biopharmaceutical company dedicated to creating extraordinary medicines for people living with cancer, reported updates from its targeted first-in-class oncology programs at the 43rd Annual J.P. Morgan Healthcare Conference in San Francisco (Press release, Parabilis Medicines, JAN 14, 2025, View Source [SID1234649732]).

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The presentation by Mathai Mammen, M.D., Ph.D., Chairman and CEO of Parabilis Medicines, highlighted recent advances in the Company’s versatile and tunable Helicon platform. This powerful peptide platform is capable of entering cells and potently and selectively binding proteins where small molecules cannot, drugging otherwise undruggable targets. Recent technical breakthroughs have led to an expanded range of powerful applications for Helicons across three main areas: functional inhibitors of intracellular protein-protein interactions, targeted protein degraders, and targeted radiopharmaceuticals. Additionally, the Company provided an update from its lead program, FOG-001, which is being evaluated in an ongoing Phase 1/2 study for microsatellite stable (MSS) colorectal cancer and other Wnt-pathway activated (WPAM+) solid tumors.

"We’ve made significant leaps forward in the last year in both experimental and data science technologies, propelling us toward an even deeper understanding and practical applications of the unique capabilities of Helicon peptide therapeutics," said Dr. Mammen. "Promising data from our ongoing Phase 1/2 trial show that FOG-001 is a bona fide β-catenin TCF4 inhibitor, confirming Helicons’ ability to target proteins previously considered undruggable in patients. FOG-001 could represent an expansive opportunity with the potential to provide benefit across multiple common cancer types, including colorectal cancer. We expect 2025 to be an eventful year, including the planned presentation of FOG-001 clinical results and the advancement of additional first-in-class pipeline programs including our ERG degrader for prostate cancer toward the clinic."

Program Updates and Expected 2025 Milestones

FOG-001

FOG-001 is the first and only direct inhibitor of β-cateninTCF4, which drives the vast majority of colorectal cancers and plays a significant role in several other cancer types. FOG-001 is currently being evaluated in a Phase 1/2 clinical trial (NCT05919264), and more than 60 patients with locally advanced or metastatic solid tumors have been dosed to date.

Early clinical data for FOG-001 confirm monotherapy antitumor activity with a manageable safety profile. Furthermore, paired biopsy transcriptomic and immunohistochemistry analyses have confirmed FOG-001’s in-tumor target engagement, eliciting important biological changes within the tumor microenvironment, including increased markers of inflammation, decreased markers of stemness, and increased markers of cellular differentiation. These clinical observations, coupled with preclinical data, provide a strong biological rationale for continued development of FOG-001 as a monotherapy and for evaluating multiple combination cohorts. Preliminary Phase 1/2 data are expected to be shared publicly in 2025.

ERG Degrader

The presentation also featured first-in-industry data demonstrating in vivo degradation of ERG, a longstanding high-value target in prostate cancer. ERG fusions have been implicated in 40-50% of all prostate cancer cases, and a Helicon-based targeted ERG degrader could provide a novel therapeutic option for patients with metastatic castrate-resistant prostate cancer (mCRPC). In vivo proof-of-concept data in preclinical models of prostate cancer showed robust activity with coincident ERG degradation confirmed by immunohistochemistry. The Company’s ERG degrader program is expected to advance into IND-enabling activities in 2025.

Radioligand Therapies

In May 2024, Parabilis Medicines and ARTBIO announced a collaboration to co-develop Helicon-enabled alpha radioligand therapies (HEARTs) incorporating the potential best-in-class isotope Lead-212 (also called 212Pb). The Company has identified multiple Helicons with sub-nanomolar affinity for the lead target. The collaboration continues to rapidly advance programs against multiple novel radioisotope targets.

About FOG-001

FOG-001 is an investigational first-in-class competitive inhibitor — and the only direct inhibitor — of β-catenin interactions with the T-cell factor (TCF) family of transcription factors, and is currently in clinical development. By directly targeting the β-cateninTCF4 protein-protein interaction, the most downstream node in the Wnt pathway, FOG-001 is intended to block the Wnt signaling pathway irrespective of the particular mutations driving disease.

FOG-001 combines key features that distinguish it from previously reported Wnt/β-catenin pathway modulators: FOG-001 acts inside the cell where it binds directly to the key oncogenic driver β-catenin; and FOG-001 blocks the Wnt pathway at the most downstream node, disrupting the interaction between β-catenin and the transcription factor TCF, thereby abrogating the signal transmission by which Wnt pathway mutations are believed to drive oncogenesis. FOG-001 is currently being evaluated in a first-in-human Phase 1/2 clinical trial in patients with locally advanced or metastatic solid tumors.

On January 14, 2025 Adimab, LLC, the global leader in the discovery and engineering of fully human monoclonal and multispecific antibodies, reported that five therapeutic products containing molecules discovered or optimized by Adimab have been approved for commercial sale (Press release, Adimab, JAN 14, 2025, View Source [SID1234649731]). Adimab’s first partnered program to receive approval was Innovent’s TYVYT (sintilimab injection), which is currently marketed by Innovent and Lilly in China for seven cancer indications.

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Other commercial products containing molecules from Adimab include:

Innovent’s SINTBILO (tafolecimab injection), a PCSK9 program approved in China for the treatment of adult patients with primary hypercholesterolemia and mixed dyslipidemia.
IASO Bio’s FUCASO (equecabtagene autoleucel), a BCMA CAR-T program approved in China for the treatment of patients with multiple myeloma.
Invivyd’s PEMGARDA (pemivibart), a SARS-CoV-2 monoclonal antibody approved for prophylactic emergency use to prevent COVID-19 infection in the United States.
Checkpoint Therapeutic’s UNLOXCYT (cosibelimab) received BLA approval December 2024 in the United States for multiple myeloma.
There are 11 additional Adimab-associated programs that are currently in Phase II or Phase III (pivotal) trials. The total number of Adimab-associated clinical programs initiated by our partners has now reached 78.

"Helping our partners get new therapies on the market to treat patients has been our goal from day one," explained Ryan McGovern, Chief Financial Officer of Adimab. "Given our high number of currently-approved and late-stage programs, we made the decision in 2024 to move royalty rights on our more advanced assets into a separate business unit called Adimab Royalty Company (ARC), which provides a unique opportunity for investors interested in an advancing, diversified portfolio of royalty-bearing assets. The rapid clinical and commercial advancement of so many exciting therapies is driving the value of ARC in addition to validating our core business at Adimab, which remains focused on generating new therapeutic candidates for our partners."

"Therapeutic product development has many challenges, and it is truly meaningful when programs are approved and reach patients. Over time, we have succeeded in building a valuable, sustainable business because of our relentless focus on high-quality execution for our partners without the distraction and conflict of an internal development pipeline. Also critical to our success are our continuous investment in improving the Adimab platform, our discipline on the expense side, our highly talented and committed employees, and our supportive investor base," said Philip T. Chase, Chief Executive Officer of Adimab. "We have been a reliable collaborator since 2009 and those looking to discover protein-based therapeutics know that we will continue to be a dependable resource for years to come."

Adimab partners have exercised more than 115 commercial licenses to option rights to advance programs into clinical development. In 2024, 11 partners exercised commercial options including BMS, NextPoint, Regeneron, REGiMMUNE, SixPeaks Bio, Santa Ana Bio, Triveni Bio, and Werewolf, among others.

Technologies

Antibody Discovery: Adimab discovers therapeutic antibodies in IgG and VHH formats through our proprietary yeast-based technology. Adimab can utilize its fully human synthetic diversity as well as additional diversities from in vivo sources. Antibodies from Adimab have exquisite specificity and are utilized in a variety of modalities, including monoclonal and multispecific formats, CAR-Ts, ADCs, etc.

Engineering: Adimab has developed and refined its engineering capabilities over thousands of lead antibody optimization efforts. The process starts with one or more partner-selected lead antibodies with the goal of optimizing potency, specificity, and/or developability. In addition to Adimab-discovered antibodies, engineered antibodies can originate from outside sources, typically to fix undesirable properties of antibodies from in vivo and phage-based technologies. Adimab also applies its engineering expertise to cytokines, TCRs, and other proteins.

Multispecifics: Adimab has extensive bispecific and multispecific know-how and capabilities, including proprietary solutions for both Fc (HC:HC) and Fab (HC:LC) heterodimerization, to allow for the generation of numerous bispecific and multispecific product designs with excellent developability properties. Additionally, Adimab can perform common light chain and fragment-based discovery and engineering necessary for certain partner-desired formats.

T Cell Engagers: Adimab has a highly characterized suite of functional and diverse CD3 (both IgG and VHH binders) and CD28 antibodies to generate bi- and multi-specific T cell engagers. Adimab has partnered this program non-exclusively with more than 25 partners, to date.

Complex Targets: Certain membrane-obligate proteins (e.g., GPCRs and ion channels) are often poorly behaved outside their native membrane environment. For these targets, Adimab has developed proprietary in vitro and in vivo discovery workflows that rely solely on the target being expressed in its native membrane and without the need for antigen mimetics. The company has employed these workflows numerous times to generate robust panels of functional and specific antibodies to these classically difficult targets, which are then further extensively engineered with our yeast platform.