Azeliragon

iStock, Andrii Yalanskyi The platform strategy of using one molecule to target an underlying biological pathway to address many different diseases can be a goldmine for smaller companies. But it also has a unique set of challenges, not least of which is the budgetary and operational strain that come with clinical development across many indications. From 2012 to 2020, AbbVie’s I&I blockbuster Humira reigned as the most valuable drug in the world . Sales peaked in 2022, when the biologic brought in $21.2 billion and became the highest-grossing drug of all time . Now, after losing patent protection and market share to biosimilars, Humira has ceded the throne to Merck’s PD-1 inhibitor Keytruda, which last year hit upwards of $29 billion in revenue , comfortably beating all its competitors. The market dominance of these two drugs was driven by several factors, but there is one crucial similarity between them: Both are what pharma analytics firm Evaluate calls pipelines-in-products. That is, drugs from which “several chronic disease indications can be squeezed out.” In order for a molecule to be a good pipeline-in-a-product candidate it must target “fundamental biological processes . . . that underlie multiple disease states,” BioPharmCatalyst senior director John Gagliano told BioSpace in an email. Immune cascades, cellular checkpoints and metabolic pathways are good examples of these processes. There should also be a “clear biological rationale” that links the biological pathway the asset is targeting to the diseases it seeks to address, he added. But broad mechanistic applicability is just the beginning. A good pipeline-in-a-product should also have “compelling clinical differentiation” as well as a “strong safety profile,” which in turn will allow its investigation across different populations, Gagliano explained. If a molecule ticks all these boxes and clears all regulatory hurdles, it could be a big commercial boon. “In today’s therapeutic landscape, these products typically unlock the power of combination therapies,” Ken Krisko, partner and head of Life Sciences Corporate Partnering and Licensing at Cooley LLP, told BioSpace in an email. The platform strategy also comes with “the potential for extended revenue over time,” Krisko continued, allowing companies to “place larger bets on the development and manufacturing infrastructure” for these molecules. If approved, he added, pipeline-in-a-product assets “offer unparalleled ability to combine commercialization strategy and improve leverage in payer negotiations.” Of course, these are all only true if the company can execute in the market. And on that front, this platform approach comes with a unique set of barriers and challenges, especially for smaller companies, including the operational strain that comes with running drug development and commercialization in parallel. Less-established players will need to “navigate a crowded competitive landscape, supporting each new indication while allocating resources strategically to avoid internal competition between launches,” according to Krisko. “The key is recognizing that while these assets offer tremendous opportunity, they require sustained strategic commitment and excellent execution across multiple launches,” Gagliano told BioSpace . In this piece, BioSpace reviews up-and-coming pipeline-in-product molecules, going beyond the Keytrudas and the Humiras—even past the GLP-1s—to focus on assets from smaller players that are taking on big risk for a huge potential reward. Cantex Harnasses RAGE for Cancer, Respiratory Cantex Pharmaceuticals is leveraging the pipeline strategy to address diseases across more than one therapeutic area. The Florida biotech is building its business on the small-molecule drug azeliragon, which according to CEO Stephen Marcus is “relevant to a broad range of illnesses.” Azeliragon targets a central receptor called RAGE, which “has been strongly implicated in the initiation and progression” of many different common cancers and lung conditions, Marcus explained to BioSpace in an email. In line with this activity, Cantex is advancing the drug for pancreatic cancer, breast cancer and glioblastoma, as well as for brain metastasis from different primary malignancies . The FDA in December 2024 granted azeliragon orphan drug designation for brain metastasis from breast cancer. Cantex is also working on respiratory indications, including severe asthma and advanced chronic obstructive pulmonary disease. Of these, the most mature program for azeliragon is in severe pneumonia. A Phase III study —which was originally in COVID-19 but later expanded to include all hospitalized pneumonia patients—will test whether azeliragon’s RAGE action can prevent acute kidney injury, a common complication that can lead to death in these patients. The study is ongoing and has a primary completion date in April next year . But while azeliragon’s mechanism gives Cantex “multiple options for clinical development,” Marcus said that small companies like his still face the “risk that a lack of focus will produce insufficient evidence of effectiveness across” all of its potential indications. “Careful selection of the disease targets based on likelihood of efficacy, the cost of clinical trials, and the need for such a therapy are crucial,” he added. Cognition Focuses on Neuro With Zervimesine Whereas Cantex is looking to apply its platform strategy across a diverse set of therapeutic areas, New York– and Pennsylvania-based Cognition Therapeutics is leaning into the neurodegenerative space. Zervimesine is an orally available drug that works by targeting the sigma-2 receptor. This mechanism, according to CEO Lisa Ricciardi, is “functionally distinct from other approaches for neurodegenerative diseases” and allows zervimesine to “displace” toxic amyloid-beta plaques from the spaces between neurons, in turn preventing damage and potentially slowing cognitive decline. Cognition is proposing the drug for Alzheimer’s disease, dementia with Lewy bodies and geographic atrophy secondary to age-related macular degeneration, with recent data underlining the therapeutic potential of zervimesine for all three conditions. At the 2025 Alzheimer’s Association International Conference in June, results from the Phase II SHIMMER trial showed that in patients with dementia with Lewy bodies, zervimesine improved neuropsychiatric, cognitive, motor and functional performance. Also at AAIC 2025, the Phase II SHINE trial found that zervimesine could arrest further cognitive deterioration in patients with mild or moderate Alzheimer’s disease. Cognition has completed a “ productive ” end-of–Phase II meeting with the FDA for zervimesine in this indication. Similarly, the mid-stage MAGNIFY trial documented slower lesion growth in patients with geographic atrophy. “To our knowledge, there is no other agent which has shown positive Phase II results across these disease entities,” Ricciardi told BioSpace in an email. For smaller players like Cognition, Ricciardi said that pipelines-in-products such as zervimesine offer a “strategic advantage” by allowing for “resource optimization” while also giving the companies access to a “broadened market potential.” Airway Focuses on the Lungs With Zelpultide Alpha For Marc Salzberg, CEO and chief medical officer of Airway Therapeutics, a good pipeline-in-a-product must possess at least one of two key characteristics. It should either address underlying mechanisms for multiple conditions or have multiple properties. “In the case of zelpultide alpha, both apply,” Salzberg told BioSpace in an email. Zelpultide alpha is a recombinant human protein that works by mimicking the endogenous protein SP-D, a lung surfactant that under healthy conditions helps clear pathogens from the lungs while also minimizing inflammation. This mechanism of action allows zelpultide alpha to modulate pulmonary inflammatory and immune responses, while also reducing bacterial, fungal and viral infections, according to Airway’s website . The Ohio biotech is primarily testing zelpultide alpha for bronchopulmonary dysplasia (BPD) in infants, for which it launched a global Phase III study in December 2024. The trial aims to enroll more than 300 preterm infants who lack SP-D in their lungs. Phase Ib data, presented May 2024 , showed that zelpultide alpha lowered BPD incidence in preterm neonates versus air sham, while also reducing the need for mechanical ventilation. “It is essential to design a development program which is prioritized,” Salzberg explained to BioSpace , adding that small companies like Airway “cannot afford to develop a platform therapy across multiple indications in parallel.” In choosing BPD as its priority indication, Airway looked at the strength of the data backing zelpultide alpha, the level of medical need and the competitive landscape, he added. Still, Airway plans to capitalize on zelpultide alpha’s broad potential for respiratory indications. The biotech is also testing the molecule for community-acquired pneumonia, for which it is in early-stage development. In addition, the company sees zelpultide alpha’s therapeutic potential for asthma, chronic obstructive pulmonary disease and acute respiratory distress syndrome, as per Airway’s website . The first two indications mirror another famed pipeline in a product, Regeneron and Sanofi’s blockbuster Dupixent . Diakonos Chases Keytruda With a Dendritic Cell Vaccine With Keytruda currently reigning as king of the biopharma industry, many smaller players are looking to follow in its footsteps and develop drugs that can be used across a wide variety of oncology indications. One of these is Houston-based Diakonos Oncology, which is working on a dendritic cell vaccine called dubodencel. Part of the immune system, dendritic cells work by processing antigens—parts of a virus, for example, or bits of a tumor—to other immune players, in turn triggering an anti-cancer response. Diakonos is taking advantage of this pathway with a vaccine that uses a patient’s own cancer antigens to trigger a “powerful and natural immune response” against the cancer, according to the biotech’s website . Diakonos is advancing dubodencel in a Phase II trial for glioblastoma, with the first patient dosed last month . Phase I data in June showed that vaccination led to significant expansion of CD4+ and CD8+ memory T cells, with side effects being mostly mild. At 12 months, the overall survival rate was higher than the standard of care. For smaller companies like Diakonos, pipeline assets such as dubodencel “inevitably involve higher upfront complexity and costs,” CEO Jay Hartenbach told BioSpace in an email. In May, the biotech raised $20 million to support the development of dubodencel in glioblastoma, but even with this added infusion, Diakonos is approaching the drug’s development with discipline. “Success goes hand in hand with disciplined sequencing of trials,” Hartenbach said, noting that by wisely planning trials, companies can “leverage strategic partnerships for specific indications,” such as through combo studies. “Being able to target multiple indications does not mean the company should pursue them all at once,” he said. Immunophotonics Targets Solid Tumors With Injectable Polymer Like Diakonos, Missouri-based Immunophotonics is also chasing after Keytruda with IP-001 , a glycan polymer that functions both as an antigen depot and an activator of the immune system. Owing to its structure, IP-001 helps retain antigens at the injection site and prolongs their exposure to immune cells. The molecule also attracts antigen-presenting cells, facilitating their activation, in turn triggering strong downstream immune responses. “The versatility of IP-001 lies in its ability to be paired with various local treatments,” which in turn converts these procedures—such as photothermal therapy and tumor ablation—“into an immunologically active event,” Cooley’s Krisko told BioSpace. “One platform, multiple therapeutic avenues.” Lu Alleruzzo, CEO and co-founder of Immunophotonics, told BioSpace in an email that platform assets like IP-001 need a development strategy that takes “expansion and alternate use into account.” The biotech is putting this into practice with its INJECTABL clinical program, which is testing IP-001 in various solid tumors, including colorectal cancer, soft tissue sarcoma and non-small cell lung cancer. Last month, the company announced that the final patient had been dosed in INJECTABL-1, a Phase Ib/IIa trial in 41 patients with advanced disease. INJECTABL-3 will test IP-001 plus ablation treatments in certain key indications for which ablation is the current therapeutic standard, as per a September 2024 news release . Small biotechs should also consider external partnerships, Alleruzzo added, for “effective execution of pipeline expansion.” Partners could also open up combination regimens. Immunophotonics is also running the Phase II/III INJECTABL-3 trial in collaboration with the Cardiovascular and Interventional Radiological Society of Europe, which will nominate a steering committee to help with the study design, as well as leverage its contract research organization Next Research.