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Analyst Upgrade Boosts Shattuck On Confidence In Next-Gen Inflammatory Bowel Disease Therapy

BenzingaDecember 01, 2025 at 9:33 PMFull Content
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Detected Companies & Sentiment

Merck & Co., Inc.
"positive outlook"
8

Gist

Analyst upgrade to Buy on Shattuck Labs (STTK) reflects confidence in its novel DR3 antagonist SL-325 for IBD, highlighting differentiation from competitors and strong clinical potential.

LLM Summary

HC Wainwright upgraded Shattuck Labs (STTK) to Buy from Neutral with a $6 price target, citing the company’s innovative DR3 antagonist SL-325 as a promising next-generation IBD therapy. The Phase 1 trial is underway, with SAD and MAD enrollment expected by Q2 2026. The analyst emphasizes SL-325’s potential to overcome immunogenicity issues seen in TL1A-targeting drugs from Merck and Roche. STTK stock rose 13.3% to $2.38 following the upgrade.

Full Article Content

HC Wainwright upgraded Shattuck Labs Inc. (NASDAQ: STTK) from Neutral to Buy, with a price forecast of $6. The company’s lead product candidate, SL-325, is a DR3 antagonist antibody for inflammatory bowel disease (IBD).

The company dosed the first healthy participants in the single-ascending dose (SAD) portion of the Phase 1 clinical trial in the third quarter of 2025.

Enrollment of SAD and multiple-ascending dose (MAD) portions is expected to be completed in the second quarter of 2026.

“We see an opportunity for SL-325 to enter and take up significant market share,” analyst Joseph Pantginis wrote on Monday.

Several competitors are currently later in development and have established clinical proof-of-concept with the TL1A approach, he added. But one key lingering concern that remains with their shared MoA is immunogenicity.

The TL1A/DR3 development landscape for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s Disease (CD), has been a popular (including Big Pharma) signaling axis to target, but only the TL1A side of the axis with ligand blocking mAbs.

Merck & Co. Inc.’s (NYSE: MRK) tulisokibart and Roche Holdings AG’s (OTC: RHHBY) afimkibart are among the leading late-stage TL1A programs, with encouraging data so far. However, the durability of response and rising concerns around immunogenicity and anti-drug antibodies remain common constraints across the class.

Shattuck aims to differentiate by targeting the opposite side of the pathway—DR3—with its candidate SL-325. While receptor-level targeting has historically been more complex than blocking the soluble TL1A ligand, Shattuck's antibody-engineering capabilities have allowed it to effectively antagonize DR3, where others have struggled.

Because DR3 is constitutively expressed, blocking the receptor is expected to deliver more durable inflammatory control than ligand-level inhibition, given TL1A's transient, inflammation-driven expression in the gut.

Price Action: STTK stock is up 13.3% at $2.38 at the last check on Monday.

Metadata

Author:
Vandana Singh
Image URL:
https://cdn.benzinga.com/files/imagecache/250x187xUP/images/story/2025/12/01/Doctor-In-A-White-Coat-Hands-Holding-Sto.jpeg
Tickers:
MRK, RHHBY, STTK
Updated At:
December 01, 2025 at 5:33 PM
Benzinga Channels:
Analyst Color, Biotech, News, Upgrades, Health Care, Analyst Ratings, Movers, Trading Ideas, General
Benzinga Tags:
Expert Ideas, why it's moving
Teaser:
HC Wainwright upgrades Shattuck Labs on confidence in SL-325, a DR3 antibody aiming for stronger, durable IBD treatment amid TL1A concerns.
Benzinga Stocks:
MRK (NYSE), RHHBY (OTC), STTK (NASDAQ)
Benzinga Article ID:
49148950