1. SELLAS Life Sciences Group (NASDAQ:SLS)

Year-to-date gain: 210.19 percent
Market cap: US$477.18 million
Share price: US$3.35

SELLAS Life Sciences Group is a late-stage biopharmaceutical company focused on novel cancer immunotherapies. The company’s approach involves ‘teaching’ the immune system to recognize and kill cancer cells by targeting specific proteins that are overexpressed in tumors.

Its flagship asset is galinpepimut-S (GPS), a vaccine-like immunotherapy for patients with acute myeloid leukemia (AML) who are in remission but at high risk of relapse. Its secondary asset, SLS009, is a highly selective CDK9 inhibitor currently showing promise in Phase 2 trials for various blood cancers.

The company’s stock price surged on December 29 after SELLAS shared an update on the Phase 3 REGAL trial evaluating GPS as a maintenance therapy in patients with AML. The trial is designed as a blind survival study, with the end point triggered on the 80th patient death.

In the update, the company reported that 72 deaths had occurred as of December 26. Because it is taking longer than expected for the trial to complete, which was previously anticipated to happen before the end of 2025, investors are speculating that the patients in the trial are living significantly longer than the historical average.

2. IO Biotech (NASDAQ:IOBT)

Year-to-date gain: 129.47 percent
Market cap: US$144.28 million
Share price: US$2.16

IO Biotech is developing immune-modulating therapeutic cancer vaccines based on its T-win technology platform, designed to activate T cells to target both tumor cells and the immune-suppressive cells.

The clinical-stage biopharmaceutical company’s lead cancer vaccine candidate is IO102-IO103, which has the brand name Cylembio. IO102-IO103 has breakthrough therapy designation from the US Food and Drug Administration (FDA) when used in combination with Merck’s (NYSE:MRK) anti-PD-1 therapy Keytruda for the treatment of advanced melanoma based on positive Phase 1/2 first line metastatic melanoma data.

The candidate reached a major milestone in August 2025 with the readout of its pivotal Phase 3 trial of IO102-IO103 with Keytruda for treating advanced melanoma. While the vaccine combined with Keytruda showed a significant survival benefit — reaching 19.4 months of progression-free survival compared to 11 months for Keytruda alone — it narrowly missed the strict statistical significance threshold.

Following a December meeting with the FDA to discuss a path forward for Cylembio, IO Biotech ended the year focused on a new registrational trial to address the Phase 3 miss and securing further funding to extend its operations into 2026.

Throughout 2025, the company continued to expand its pipeline. In November, it presented new pre-clinical data for IO112 targeting arginase 1 and for IO170 targeting transforming growth factor.

3. Tiziana Life Sciences (NASDAQ:TLSA)

Year-to-date gain: 124.64 percent
Market cap: US$184.22 million
Share price: US$1.55

Tiziana Life Sciences is a clinical-stage biopharma which is developing therapies for autoimmune and inflammatory diseases, degenerative diseases and cancer-related to the liver. Its pipeline of candidates is built on its patented drug delivery technology that provides a possible alternative to intravenous delivery.

Tiziana’s lead candidate is intranasal foralumab, a fully human anti-CD3 monoclonal antibody, which it is currently studying for treatment of a range of conditions.

In March, the company filed an investigational new drug application with the FDA for a Phase 2 clinical trial in amyotrophic lateral sclerosis (ALS), which is supported by the ALS Association. The Phase 2 trial is slated to begin in January 2026. Tiziana also began dosing patients in a Phase 2a trial for multiple system atrophy in August.

In April, John Hopkins University and the University of Massachusetts commenced dosing of the biotech company’s intranasal foralumab in Phase 2 trials for patients with non-active secondary progressive multiple sclerosis (MS). On May 7, the company shared positive results from the use of its lead candidate in improving the quality of life for patients with that form of MS.

Tiziana is also studying the use of intranasal foralumab for treating moderate Alzheimer’s disease. On May 9, it announced that PET scans of a patient with moderate Alzheimer’s showed a significant reduction in microglia activation associated with neuroinflammation after three months of treatment.

On July 21, the company announced an ‘unexpected discovery’ following immunologic analysis of the patient with Alzheimer’s disease: ‘The analysis revealed an increase in phagocytosis markers in classical monocytes, suggesting that nasal foralumab may enhance their ability to clear amyloid plaques. This unexpected effect may open new avenues for treating Alzheimer’s Disease by targeting both inflammation and amyloid accumulation.’

The company dosed the first patient in its randomized Phase 2 Alzheimer’s trial in December.

To end the year, Tiazana submitted a comprehensive safety report to the FDA documenting over 37 patient-years of treatment with no serious drug-related adverse events across its studies.

4. Spero Therapeutics (NASDAQ:SPRO)

Year-to-date gain: 119.05 percent
Market cap: US$129.58 million
Share price: US$2.30

Spero Therapeutics is developing novel treatments for rare diseases and multi-drug resistant bacterial infections with high unmet need.

The company’s lead drug candidate is tebipenem pivoxil hydrobromide (HBr), a late-stage development asset developed in collaboration with pharma giant GSK (NYSE:GSK). GSK has an exclusive license agreement to commercialize the drug candidate in most markets.

Tebipenem HBr is an oral carbapenem developed to treat complicated urinary tract infections (cUTIs), including pyelonephritis. The FDA granted tebipenem HBr qualified infectious disease product and fast-track designations.

Spero’s stock surged 245 percent on May 28 to reach US$2.35 after the company reported that its Phase 3 trial evaluating tebipenem HBr for treating cUTIs met its primary endpoint and stopped early for efficacy.

On December 19, GSK officially filed the new drug application resubmission to the FDA for tebipenem HBr for treating cUTIs supported by the Phase 3 results. This filing triggered a US$25 million milestone payment to Spero that is expected in Q1 2026.

5. OKYO Pharma (NASDAQ:OKYO)

Year-to-date gain: 60.50 percent
Market cap: US$74.85 million
Share price: US$1.91

OKYO Pharma is a clinical-stage biopharma company developing therapies for the treatment of neuropathic corneal pain and dry eye disease. Its lead candidate is urcosimod, a non-steroidal anti-inflammatory and non-opioid analgesic.

OKYO is currently evaluating urcosimod for the treatment of neuropathic corneal pain. The treatment received fast track designation from the FDA in May after the company ended its Phase 2 clinical trial early to analyze data.

On July 17, the company posted strong top-line data from the Phase 2 trial and stated it is planning a meeting with the FDA to discuss next steps for its lead drug candidate. The following day, OKYO received US$1.9 million in non-dilutive funding to support its clinical development of urcosimod.

In September, OKYO announced a 120 patient, multi-center multiple ascending dose clinical trial designed to identify the optimal dose for Phase 3 registration.

A scientific breakthrough followed on December 11, when new imaging data revealed that urcosimod may actually help restore corneal nerve structure, showing median increases in nerve fiber count and length, while those in the placebo group saw median decreases for both.

1. Retail Investors Look to Trigger Silver Squeeze 2.0

Publish date: March 31, 2025

Silver received mainstream attention in March, with renewed calls for what supporters dubbed “Silver Squeeze 2.0,” reviving a theme that first gained prominence during the meme stock era of 2021.

Online chatter intensified ahead of March 31, with advocates urging coordinated purchases of physical silver to challenge what they saw as entrenched institutional control over the metal’s pricing.

Efforts traced back to a March 22 post on X by user @TheSqueakyMouse, which gained broader attention after being amplified by sector analyst Jesse Colombo. Colombo, who posts under the handle @TheBubbleBubble, has argued that the silver price is artificially suppressed by large financial institutions:

“Bullion banks like JPMorgan Chase (NYSE:JPM) and UBS Group (NYSE:UBS) suppress silver prices through aggressive naked shorting—but a coordinated surge of physical buying could catch them off guard and break their hold on the market.’

Colombo pointed to data showing that major banks hold net short positions equivalent to roughly 223 million ounces of silver, meaning a US$1 price increase could theoretically translate into US$223 million in losses for those positions.

2. Missouri Set to Recognize Gold and Silver as Legal Tender, Critics Raise Implementation Concerns

Publish date: May 12, 2025

Attention on precious metals took a more concrete form in Missouri. In May, the state’s General Assembly passed a Republican-backed amendment to a broader finance bill that recognizes gold and silver as legal tender.

The measure would require state entities to accept electronic forms of gold and silver for public debts, including taxes. Private businesses would not be required to accept precious metals, but could do so voluntarily.

Supporters argued that recognizing gold and silver offers a hedge against inflation and what they view as irresponsible federal monetary policy. Critics, however, questioned how the system would work in practice.

3. Silver Miners Deliver Record Q2 Earnings as Price Breaks Out

Publish date: August 19, 2025

Silver’s mid-year rally above US$35 per ounce translated into record or near-record earnings for many miners in Q2.

Pan American Silver (TSX:PAAS) reported record net earnings of US$189.6 million in the period, while First Majestic Silver (TSX:AG,NYSE:AG) posted its strongest quarter to date, nearly doubling revenue year-on-year.

Even mining companies facing production challenges, such as Fresnillo (LSE:FRES,OTC Pink:FNLPF), saw revenue growth driven by gold output and pricing strength.

4. Missing Silver Bars Bring Mining Community Together

Publish date: March 7, 2025

Amid those financial milestones, the mining community was united in March by a widely shared incident.

Following the Prospectors & Developers Association of Canada convention, two 10 ounce silver bars purchased by Kin Communications founder Arlen Hansen went missing after being checked in his luggage on an Air Canada flight.

The bars, worth about US$647, were intended for a silent auction benefiting Canadian children living with diabetes.

“I don’t need a refund, a free upgrade, or more points, this was stolen from the children who need it, not me,” Hansen wrote on X. The response from the mining community was swift. First Majestic Silver and its mint division volunteered to replace the lost silver, while others donated to Diabetes Canada and expressed support.

The incident also revived scrutiny of airline cargo security, particularly given Air Canada’s association with earlier high-profile precious metals thefts, including the 2023 gold heist at Toronto Pearson International Airport.

5. Pan American Silver Gets Green Light for US$2.1 Billion MAG Silver Deal

Publish date: August 25, 2025

One of this year’s most consequential silver M&A developments came when Pan American received final clearance from Mexico’s Federal Economic Competition Commission for its US$2.1 billion acquisition of MAG Silver.

The approval paved the way for the deal to close in early September, combining Pan American with one of the world’s highest-grade primary silver assets, Juanicipio.

Under the terms, MAG shareholders were to receive either cash or Pan American shares, leaving them with about 14 percent of the combined company on a fully diluted basis.

“This strategic acquisition further solidifies Pan American as a leading Americas-focused silver producer,” Pan American CEO Michael Steinmann said when the deal was announced.

He added that Juanicipio “will meaningfully increase Pan American’s exposure to high margin silver ounces,” while also providing longer-term growth through MAG’s exploration properties in Utah and Ontario.

Don Durrett: Gold, Silver Price Targets and 15 ‘Must-Own’ Silver Stocks

Kicking off the list in the fifth spot is Don Durrett of GoldStockData.com.

In this January interview, Don shared his silver and gold price outlook for 2025, as well as his 15 ‘must-own’ silver stocks. We don’t have time here for the full list, but I’ll leave the link to the video below. For now, here’s Don talking about why he’s so bullish on silver and gold stocks.

Peter Grandich: Gold Mines Set to Print Cash as Price Hits New Highs

Peter Grandich of Peter Grandich & Co. is next.

This interview is from all the way back in February, when gold was still around US$2,800 per ounce. Peter talked about how US$5,000 was no longer sounding outlandish to him, and also explained how the higher gold price could impact mining companies.

Vince Lanci: Silver’s London Liquidity Crisis — What’s Happening, What’s Next

Vince Lanci of Echobay Partners is always a popular guest, and in mid-October he helped break down unusual dynamics in silver, which had broken through US$50 per ounce.

Ed Steer: Silver Rally Now Unstoppable, Price to Hit Triple Digits

Ed Steer of Ed Steer’s Gold and Silver Digest comes in at number two. This interview is also from mid-October, and in it Ed weighed in on the silver market’s complex inner workings. Ed also gave his thoughts on the precious metal’s long-term prospects.

Rick Rule: Gold Strategy, Oil Stocks I Own, ‘Sure Money’ in Uranium

Finally, our most popular interview of 2025 was with none other than Rick Rule of Rule Investment Media. In this early November conversation, he said he had recently sold 25 percent of his junior gold stocks; he also explained why he did it and how he redeployed that capital.

Capex digestion and AI verticalization

AI capital expenditures by hyperscalers are projected to fuel demand for semiconductors, data centers and related infrastructure in the year head, as per Nicholas Mersch, portfolio manager at Purpose Investments.

According to notes from multiple analysts, the Big Four — Meta Platforms (NASDAQ:META), Microsoft (NASDAQ:MSFT), Alphabet (NASDAQ:GOOGL) and Amazon (NASDAQ:AMZN) — are slated to spend over US$300 billion on AI infrastructure. Mersch cited forecasts that see hyperscaler capex hitting roughly US$600 billion in 2026.

“Over the next 12 to 24 months, the narrative likely shifts from who can build fastest to who can drive the highest revenue and margin per dollar of AI infrastructure,’ Mersch added. “This is where verticalization matters. The companies that can capture the full stack, from silicon to applications, look like they will win.’

His top pick in this arena is Google, followed by Microsoft.

While the cloud layer remains a high-stakes game of concentration among a few platforms, Mersch said the hardware layer underneath is beginning to fragment as the chip stack quietly diversifies.

“Large multi-year AI chip deals are broadening the market beyond NVIDIA (NASDAQ:NVDA), with Advanced Micro Devices (NASDAQ:AMD) and custom application-specific integrated circuit (ASIC) programs winning meaningful share. High-bandwidth memory (HBM) has become the real bottleneck and profit pool, with tri-sourced HBM3E, an emerging HBM4 race and surging HBM demand from ASICs,’ the expert said.

‘The result is a more plural, multi-vendor accelerator ecosystem. Looking out to the second half of the decade, total AI silicon spend can keep growing even if individual GPU vendors see more competition and pricing pressure, with memory, packaging and custom silicon capturing a larger share of the economics.’

Chip diversification, however, is now colliding with HBM and packaging shortages, constraining output from 2026 to 2027. BMI’s Cedric Chehab notes that rapid capex growth is outpacing supply, ruling out near-term oversupply, but warns of volatility if data center investments fail to deliver profitability amid persistent infrastructure shortages.

Investor takeaway

The investment focus in AI is shifting from the initial narrative to tangible execution and quantifiable profitability. While the challenges of elevated valuations and geopolitical instability persist, some experts dismiss comparisons to a technology bubble, arguing the sector’s demonstrated value offers a stable underpinning.

Future leaders in the AI industry will be distinguished by their capacity to convert infrastructure spending into significant operating leverage and cost efficiencies.