Two Bets on Immune Selectivity Land the Same Day
Two biotech bets on the same week: Neomorph closes $100M to push molecular glues into the clinic, and Spyre posts Phase 2 ulcerative colitis data that positions its gut-selective antibody as a potential upgrade to a $5 billion drug.
The stories landed within hours of each other, and the timing is more than coincidence. Both programs rely on the same underlying biology: selectively removing or blocking immune cells from doing damage. They represent opposite ends of the drug discovery spectrum. One is a molecular glue degrader, a chemistry-first approach to eliminating disease-driving proteins that conventional small molecules cannot touch. The other is an engineering play: taking a proven target and using antibody design to make it work better.
Neomorph, based in San Diego, announced the closing of its $100 million Series B on Monday. The round was led by Deerfield Management, with Regeneron Ventures, Longwood Fund, Alexandria Venture Investments, and Binney Street Capital of Dana-Farber Cancer Institute joining as new investors. The company has now raised $100M Series B to fund its lead program, NEO-811, a first-in-class molecular glue degrader targeting ARNT (also known as HIF-1β) in clear cell renal cell carcinoma, currently in a Phase 1/2 trial. But the oncology asset is not the whole story. Neomorph's platform is built around engineering neomorphic protein surfaces that redirect the cell's own protein disposal machinery (the E3 ubiquitin ligase system) to eliminate targets that have been considered undruggable. The company has signed partnership deals with Novo Nordisk, Biogen, and AbbVie spanning cardiometabolic disease, rare disease, neurology, oncology, and immunology, which gives it a pipeline that extends well beyond a single kidney cancer trial.
That sprawling deal activity is worth noting. Molecular glue degraders have been validated in the clinic, with lenalidomide and related IMiD agents standard of care in multiple myeloma for years. But the field has struggled to move beyond lucky chemistry toward rational design. Neomorph's pitch is that it has solved that problem. "We believe that Neomorph has built a differentiated platform with the scientific depth to systematically access a vast new target space", said Cam Wheeler, a partner at Deerfield and chair of Neomorph's board. Whether that holds up in Phase 2 is an open question, but the company has bought itself enough runway to find out.
Spyre Therapeutics, meanwhile, released the first dataset from its Phase 2 SKYLINE trial on Monday morning, and the numbers are clean. SPY001, an extended half-life antibody targeting the α4β7 integrin, hit the primary endpoint in patients with moderate-to-severe ulcerative colitis: a statistically significant 9.2-point reduction in the Robarts Histopathology Index score at 12 weeks (p<0.001). Forty percent of patients achieved clinical remission by modified Mayo Score, and 51% showed endoscopic improvement. The safety profile was consistent with the α4β7 class, with no drug-related serious adverse events and no discontinuations due to adverse events. The trial enrolled 43 patients in Part A.
The α4β7 target is the same one underpinning Takeda Pharmaceutical's Entyvio, which posted roughly $5.4 billion in global sales in 2025 and has become a backbone of biologic treatment for inflammatory bowel disease. Spyre is not the first company to go after this pathway, and it will not be the last. What makes SPY001 potentially differentiated is its half-life engineering: Spyre designed the antibody to have extended exposure, which could mean less frequent dosing and higher induction concentrations relative to vedolizumab. The company framed the data as supporting a "best-in-class" profile on the basis of matching vedolizumab's epitope and potency while improving pharmacokinetics.
"We designed SPY001 to improve upon vedolizumab's proven activity in IBD by matching its epitope and potency while increasing target coverage through an extended half-life and greater induction dosing", said Deanna Nguyen, Spyre's SVP of clinical development. The Phase 2 results bear that hypothesis out on the primary endpoint, but comparisons across trials are treacherous. Head-to-head data do not yet exist, and the open-label Part A design limits what can be concluded about relative efficacy.
The more interesting story may be Spyre's platform structure. SKYLINE is built as a two-part induction and maintenance trial testing not just SPY001 alone but SPY002 (anti-TL1A), SPY003 (anti-IL23), and pairwise combinations, six investigational agents total. Part A was an open-label monotherapy screen. Part B is randomized and placebo-controlled, testing two dose levels of each monotherapy and three combination regimens (SPY120, SPY130, SPY230). The gut-selective α4β7 mechanism is being positioned as an ideal backbone for combination therapy with cytokine-targeting antibodies. Part B enrollment is now open, with induction data expected in 2027. SPY002 proof-of-concept data are expected mid-2026, and SPY003 data in Q3 2026.
For investors tracking the IBD landscape, Spyre's dataset lands in a crowded field. AbbVie has Rinvoq (upadacitinib) in the JAK class with broad IBD approvals. Eli Lilly has mirikizumab (anti-IL-23p19) approved for ulcerative colitis. Pfizer has etrasimod in the S1P receptor modulator class. And across all of these, vedolizumab remains entrenched. Spyre needs not just a good drug but a compelling combination story to justify a competitive entry.
What connects these two stories beyond the calendar is the therapeutic logic. Both Neomorph and Spyre are betting that selectively modulating the immune system (taking out specific proteins or blocking specific cell trafficking pathways) will work better than the blunt instruments that came before. Neomorph's approach is irreversible and catalytic: one molecular glue molecule can guide the destruction of many copies of a target protein. Spyre's is engineered reversibility: an antibody that binds α4β7 and blocks immune cell homing to the gut, then clears over time. Both are technically sophisticated. Both face the same long odds of Phase 3.
But the funding environment for molecular glue degraders and long-acting biologics has improved markedly since the dark days of 2022 and 2023. Neomorph's $100M round, with Regeneron Ventures participating, signals that big pharma sees the platform potential, not just the oncology asset. And Spyre's dataset gives the field a concrete data point to anchor combination therapy speculation. Whether either bet pays off is a question for the clinic. For now, the bets are on the table.
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