Investing in Innovation: Four Small-Caps Driving the Future of Pain Therapy (NTRB, COLL, ASRT, AQST)

The global transdermal patch market is quietly gaining ground. Valued at $7.8 billion in 2023, it is projected to reach nearly $10.95 billion by 2030. Within that, pain patches are leading the way, expected to grow from $4.8 billion in 2021 to $7.3 billion by 2031.

But this growth is not just about convenience. Transdermal drug delivery is solving critical problems, from managing chronic pain in aging populations to delivering medications without needles. Most importantly, it offers a safer alternative to traditional opioid use.

The abuse-deterrent opioid segment, while still relatively small, is gaining momentum. It is projected to more than double between 2024 and 2030, driven by regulatory pressure, clinical demand, and advances in technology. That convergence is starting to attract serious investor interest.

This creates a promising setup for small-cap biopharma companies focused on innovative pain and rescue therapies. Several are moving closer to meaningful catalysts such as New Drug Application submissions and early-stage commercial progress.

Here are a few stocks positioned to benefit from this overlooked but vital shift in drug delivery.

Nutriband Inc. (NASDAQ: NTRB) is positioning itself as a disruptive force in the opioid pain management space with its lead product candidate, AVERSA Fentanyl, a transdermal patch designed to deter abuse, misuse, and accidental exposure. At the core of this innovation is Nutriband's proprietary AVERSA technology, which leverages an aversive agent coating to address the most common form of fentanyl patch abuse-oral consumption. According to a 2022 market analysis by Health Advances, AVERSA Fentanyl has the potential to reach peak annual US sales of between 80 million and 200 million dollars.

Unlike many early-stage biotechs, Nutriband is generating revenue today. Through its Pocono Pharma subsidiary, which produces kinesiology tape now sold in retail giants like Walmart, Walgreens, Target, and CVS, the company recorded 667 thousand dollars in revenue in the first quarter of 2025, a 63 percent year-over-year increase. This revenue stream helps fund development and reduces dilution risk, a key differentiator in a capital-intensive sector.

Development of AVERSA Fentanyl continues to progress. Nutriband recently completed the commercial manufacturing process scale-up with its partner Kindeva Drug Delivery, a global CDMO that produces millions of transdermal patches annually. Together, they are preparing to file an Investigational New Drug application with the FDA, a crucial step ahead of the planned human abuse liability clinical study. The company is pursuing the 505(b)(2) pathway, which may allow for a faster and more efficient route to market.

Regulatory momentum is supported by growing recognition of the public health risks tied to transdermal opioid misuse. AVERSA Fentanyl is aligned with the FDA's Opioids Action Plan and has been engineered to make fentanyl patches safer without restricting access for legitimate patients. The product may also benefit from regulatory pressure to shift all fentanyl patch formulations toward abuse-deterrent formats, similar to previous changes required for oxycontin generics.

Nutriband's AVERSA platform is protected by a broad international IP portfolio with patents issued in 46 countries. Most recently, the company was granted a US patent for its transdermal abuse-deterrent system in June 2025, further strengthening its competitive moat.

Nutriband's inclusion in the Russell Microcap, Russell Microcap Growth, Russell 3000E, and Russell 3000E Growth indexes signals growing institutional awareness. Management believes this milestone reflects accelerating progress toward building shareholder value and positioning AVERSA Fentanyl as a potential category leader in opioid safety.

With real revenue, a large addressable market, strong IP, and a progressing regulatory timeline, Nutriband Inc. offers investors early exposure to a unique solution in the fight against opioid abuse.

Collegium Pharmaceutical, Inc. (Nasdaq: COLL) is quietly becoming a standout in the pain and neuropsychiatry treatment markets, driven by consistent revenue growth, expanding product reach, and shareholder-focused capital allocation. In the first quarter of 2025, Collegium reported net revenue of 177.8 million dollars, up 23 percent year-over-year, with its ADHD medication Jornay PM growing prescriptions by 24 percent and generating 28.5 million dollars in revenue for the quarter. The company has now completed a major field force expansion, bringing its ADHD sales team to approximately 180 representatives to support continued growth in this space.

The company's core pain portfolio also continues to deliver. In Q1 2025, Collegium generated 149.2 million dollars in revenue from its chronic pain medications, with each of its flagship products-Belbuca, Xtampza ER, and the Nucynta franchise-posting year-over-year growth. Belbuca alone brought in 51.7 million dollars, up 2 percent, while Xtampza ER and Nucynta added 47.6 million and 47.1 million, respectively.

Collegium's strong financial performance has supported aggressive yet balanced capital deployment. In May, the company announced a 25 million dollar accelerated share repurchase, part of a broader 150 million dollar program, reflecting confidence in its long-term value. The company ended Q1 with 197.8 million dollars in cash, up from 162.8 million at year-end 2024, and generated over 55 million dollars in cash from operations.

With reaffirmed full-year guidance, expanding leadership, and strong product execution, Collegium is establishing itself as a consistent revenue generator in the biopharma space. Its dual focus on responsibly managed pain treatments and a fast-growing ADHD franchise gives it a diversified growth engine in two high-need therapeutic areas. For investors seeking a profitable, commercial-stage biotech with upside potential and disciplined management, Collegium deserves a closer look.

Assertio Holdings, Inc. (Nasdaq: ASRT) is a specialty pharmaceutical company in transition, executing a focused strategy to strengthen its commercial platform while shedding legacy risks. In the first quarter of 2025, the company reported 26 million dollars in total net product sales, tracking in line with its full-year guidance. Management emphasized that sales from its growth assets, particularly Rolvedon and Sympazan, are outperforming internal expectations, providing a strong foundation for Assertio's near-term revenue expansion.

Assertio is actively streamlining operations and reducing legal exposure, having settled multiple longstanding lawsuits, including the DOJ False Claims Act case and opioid-related liabilities. A major structural move was the divestiture of Assertio Therapeutics, which held legacy legal obligations and low-value assets. That transaction has now fully removed Assertio Holdings and its current subsidiaries from all opioid litigation. This cleanup effort allows management to focus entirely on high-potential assets and business development.

Rolvedon, a treatment for chemotherapy-induced neutropenia, continues to show momentum, with Q1 sales outperforming despite prior-quarter inventory stocking. Management expects steady growth for the product throughout 2025. Sympazan, a prescription oral film for Lennox-Gastaut syndrome, also benefited from a revised promotional strategy, driving a 6.5 percent year-over-year increase in prescriptions during the quarter.

With a cleaned-up balance sheet, narrowed commercial focus, and a disciplined approach to portfolio expansion, Assertio is entering a new phase. The company aims to become a preferred partner in specialty pharma, leveraging its commercial infrastructure to onboard new products across therapeutic areas. For investors seeking a turnaround story with defined growth levers and reduced legal overhang, Assertio may be one to watch in 2025.

Aquestive Therapeutics, Inc. (Nasdaq: AQST) is a pharmaceutical company focused on advancing medicines that improve patients' lives through innovative science and delivery technologies. The company develops orally administered products to deliver complex molecules, offering novel alternatives to invasive standard therapies. Aquestive currently has four licensed commercial products marketed globally and serves as the exclusive manufacturer for these products. It also collaborates with pharmaceutical partners using proprietary technologies like PharmFilm and has established drug development and commercialization capabilities. The company is progressing a late-stage proprietary candidate, Anaphylm Trademark , an oral sublingual film for severe allergic reactions including anaphylaxis, alongside an early-stage epinephrine prodrug topical gel, AQST-108, targeting dermatological conditions such as alopecia areata.

In Q1 2025, Aquestive submitted its NDA for Anaphylm and is preparing for a potential U.S. launch in early 2026, pending FDA approval. The NDA includes comprehensive adult and pediatric clinical data demonstrating a pharmacokinetic profile consistent with existing epinephrine autoinjectors. Aquestive has expanded its market access and medical affairs teams and is advancing commercial readiness, including plans for regulatory submissions in key international markets. The FDA assigned a PDUFA target action date of January 31, 2026, and may convene an Advisory Committee meeting during the review process.

Sales of royalty-based products such as Sympazan Registered and Azstarys Registered contributed to revenue during the quarter, while manufacturing revenue declined due to lower Suboxone Registered volumes but was partially offset by growth in other collaborations. Total revenue for Q1 2025 was $8.7 million, down 28% from $12.1 million in Q1 2024. Research and development expenses decreased slightly, while selling, general, and administrative expenses rose primarily due to regulatory and commercial investments linked to Anaphylm's launch preparations. Aquestive reported a net loss of $22.9 million for the quarter and held $68.7 million in cash at March 31, 2025.

The company has paused sales and marketing activities for Libervant Registered following a court decision affecting its approval status, with plans to resume patient access in 2027 or sooner if permitted. Aquestive revised its 2025 revenue guidance to $44 to $50 million and non-GAAP adjusted EBITDA loss guidance to $47 to $51 million, reflecting the impact of this change.

With its innovative, non-invasive epinephrine treatment nearing regulatory approval, broad IP protection, and a clear commercial strategy, Aquestive is positioned to offer a meaningful new option for patients with severe allergic reactions and to expand its footprint in specialty pharmaceutical delivery.

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