Biotech stocks underperformed the broader market in the first half of 2021, with the iShares Nasdaq Biotechnology ETF IBB advancing about 8% year-to-date compared to the roughly 14% gain for the S&P 500 Index.

In comparison, the IBB was up 13.6% in the first half of 2020. The strength in the space in the last year was primarily due to risk aversion as the pandemic drove investors into defensive plays such as biotechs. Additionally, companies that kickstarted COVID-19 vaccine programs ran up sharply in 2020.

The relatively muted performance so far this year may have to do with the return of risk appetite leading to rotation out of the sector. The rally in vaccine stocks also moderated following emergency use authorizations being accorded for three COVID-19 shots. Here are a few stocks that stood out with solid gains amid the muted overall sector performance.

Cassava Sciences Inc (SAVA): Shares of Cassava, a neurodegenerative disease company, spiked in early February on the back of positive results from the interim analysis of data from an open-label study of simufilam, its lead drug candidate for the treatment of Alzheimer's disease. It hit an intraday high of $117.54 on Feb. 4. After pulling back and consolidating, the stock picked up pace in June. By virtue of the strong advance in the year-to-date period, the stock has tacked on about 1,150%.

Annovis Bio Inc (ANVS): This biopharma that focuses on therapies for neurodegenerative diseases has seen its shares surge by over 1, 060% so far this year. The company's lead drug ANVS401 is being evaluated for multiple indications, including Alzheimer's disease and Parkinson's disease. It works by improving axonal transport by inhibiting the neurotoxic proteins that kill nerve cells. A positive Phase 2 readout for the asset in Alzheimer's disease sent the stock soaring in late April.

Atossa Therapeutics Inc (ATOS): The Seattle-based biopharma focusing on treatments for breast cancer and COVID-19 has surged up about 770% year-to-date. From under $1 at the start of year, the stock rallied to a high of $4.90 in early February on the back of positive Phase 2 data for Endoxifen administered between diagnosis and surgery in breast cancer patients. The upward momentum faltered subsequently and the stock pulled back to a low of $1.48 on April 19.

Atossa recovered from there and the rally picked up steam in June amid the release of positive final Phase 2 data for Endoxifen and inclusion in the Russell 2000 and 3000 indexes.

Entera Bio Ltd. (ENTX): The biopharma, which develops orally delivered large molecule therapeutics for use in areas with significant unmet medical need, has seen its shares surge higher by over 460% so far this year. The company's pipeline consists of EB613, which is being evaluated for osteoporosis, and EB612 for hypoparathyroidism.

Entera Bio shares jumped in early April when it reported positive topline biomarker data for EB613. The stock received a shot in the arm from the positive six-month bone mineral density results from the Phase 2 clinical trial of EB613, which the company reported last week.

PDS Biotechnology Corp (PDSB): PDS has gained about 450% year-to-date. The company has oncology and infectious disease programs. The gains for the year-to-date period reflected the presentation of data from the Phase 2 combination study with PDS0101 in HPV-associated tumors at the ASCO conference, and also its COVID-19 program.

Anavex Life Sciences Corp. (AVXL) shares have gained about 430% year-to-date. The company is developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders.

The company's lead product candidate blarcamesine (ANAVEX2-73) is being evaluated for multiple indications. The predictive biomarker of response established with SIGMAR1 mRNA expression correlates significantly with responses in primary and secondary clinical efficacy endpoints from the proof-of-concept Phase 2 trial in Parkinson's disease, the company announced. 

Brooklyn ImmunoTherapeutics Inc (BTX): This New York-based gene and cell therapy company has clocked gains of about 375% year-to-date. The company is focused on exploring the role cytokine-based therapy can have in treating patients with cancer. The company is also exploring opportunities to advance oncology, blood disorder, and monogenic disease therapies using highly innovative gene editing/cell therapy technology.

Brooklyn initiated a mid-stage study of IRX-2 in combination with Merck & Co., Inc.'s (MRK) Keytruda and chemotherapy in triple-negative breast cancer. In March, the company completed its reverse merger with NTN Buzztime.

Howard Federoff took over as CEO in early April. Later that month, the company acquired an exclusive license for mRNA gene editing and cell therapies technology of Factor Bioscience and Novellus Therapeutics, pursuant to an exercise of a previously announced option. The company has also been added to the Russell 3000 Index.

Brooklyn's most advanced program is the study of the lead asset IRX-2, a human cell-derived biologic with multiple active cytokine components in patients with head and neck cancer. With commercialization years away — and ultimately contingent on IRX-2 clearing clinical and regulatory hurdles — the valuation of Brooklyn looks a little stretched.