Why Ventyx is Still Undervalued: The Metsera Precedent Points Above $100

Eli Lilly's $1.2 billion bid for Ventyx Biosciences represents a starting point that could ultimately lead to an acquisition price 10x higher.

Ventyx is now in the same position, except its strategic value is broader, its clinical validation stronger, and the competitive stakes are considerably higher. The $14 per share offer currently on the table may prove to be one of the most significant valuation disconnects in recent biotech M&A history.

Ventyx Bioscience’s NLRP3 inhibitors represent not only a now critical complement to existing GLP-1 therapies, but potentially a class of drugs with even broader implications for treating chronic health conditions.

Crucially, this shift is not theoretical. An NLRP3 inhibitor combined with injectable semaglutide is a product Ventyx itself could take through FDA trials. In the hands of a strategic acquirer, that same combination becomes a direct threat to existing GLP-1 franchises.

If Eli Lilly were to control VTX3232, it would not need to invent a new category to challenge Novo Nordisk. It could follow Novo Nordisk’s own regulatory path, pair semaglutide-class therapy with superior inflammation control, and undermine Novo’s core franchise using the same molecular foundation. Thus, this isn’t a question of whether a bidding war will emerge, but rather how high it will go.

The Paradigm Shift: From Weight Loss to Inflammatory Disease Treatment

The obesity market is not what it appears to be.

For years, investors have framed GLP-1 therapies as weight loss drugs—metabolic interventions that help patients shed pounds through appetite suppression and glucose regulation. But that framing is incomplete. The emerging scientific consensus points to a more fundamental mechanism: obesity is, at its core, a state of chronic systemic inflammation.

If obesity equals chronic inflammation rather than simple metabolic dysfunction, then the entire $150 billion obesity market transforms into something far larger: a gateway to treating the inflammatory cascade underlying cardiovascular disease, neurodegeneration, liver disease, and autoimmune conditions among others. Weight loss becomes a symptom of successful treatment rather than the treatment itself.

Ventyx's VTX3232 sits at the center of this paradigm shift. The NLRP3 inflammasome operates as a central switch governing inflammatory cascades across virtually every major chronic disease category. In Phase 2 trials, VTX3232 demonstrated 80% reduction in hsCRP, the primary biomarker for systemic inflammation and cardiovascular risk along with significant reductions in IL-6 and IL-1β.

Rather than an incremental improvement over existing therapies, this represents upstream intervention at the source of disease progression, the implications of which are profound.

If the market accepts that NLRP3 inhibitors are mandatory adjuncts to GLP-1 therapy rather than optional add-ons, then the first mover in NLRP3 plus GLP-1 combinations owns the standard of care for next-generation obesity treatment. And ultimately, NLRP3 inhibitors may supersede GLP-1s in therapeutic importance as the market recognizes their paradigm-shifting potential to treat the chronic inflammation causing heart disease, Parkinson's, liver failure, and dozens of other conditions.

Whoever wins Ventyx does not merely acquire a biotech company. They acquire the right to define how inflammation-mediated disease is treated for the next two decades.

The Existential Threat Framework: Who Loses What if Lilly Wins

Strategic acquisitions are rarely about upside. They are about preventing catastrophic competitive loss. The Ventyx situation is no different.

Every major pharmaceutical company with exposure to obesity, inflammation, or cardiovascular disease faces a simple calculation: What do we lose if Lilly combines Mounjaro with VTX3232 and we have nothing comparable?

Novo Nordisk: $50–100 Billion in Market Cap at Risk

Novo Nordisk has already lost $100 billion in market value from its 2025 peak. Lilly's Zepbound has captured dominant market share. Generic semaglutide becomes available in 40% of the world starting March 2026. CagriSema disappointed expectations.

Now imagine Lilly launches a "Complete Cardiometabolic Solution"—Mounjaro plus VTX3232—offering superior weight loss, 80% inflammation reduction, cardiovascular protection, and liver health improvement. Novo's response would be semaglutide plus a licensed or generic NLRP3 inhibitor: a me-too product, always two to three years behind.

The math is straightforward. Novo's GLP-1 franchise represents roughly 70% of enterprise value, or approximately $140 billion. Losing market leadership erodes 30–50% of that franchise value. Add the continuing share loss to Lilly, and total potential destruction reaches $60–100 billion.

Against that backdrop, paying $5–10 billion for Ventyx is a 5–10% insurance premium on a much larger potential loss.

AbbVie: The Upstream Prevention Threat

AbbVie's Skyrizi and Rinvoq franchise generated $18.5 billion in 2025 sales, growing 53% year over year, with projections reaching $31 billion by 2027. These drugs treat late-stage inflammatory diseases, such as IBD, psoriasis, rheumatoid arthritis, conditions that develop after years of chronic inflammation from obesity and metabolic syndrome.

The threat from Ventyx is existential in a different way: upstream prevention.

If VTX3232 plus GLP-1 combinations treat inflammation before it progresses to inflammatory disease, AbbVie loses its patient pipeline. Patients taking Mounjaro plus VTX3232 for weight management achieve 80% hsCRP reduction. Their IL-6 and IL-1β levels fall below disease thresholds. Fewer patients ever progress to conditions requiring Skyrizi or Rinvoq.

A 30–50% reduction in disease progression translates to $9–15 billion in annual revenue loss. Over ten years, the net present value of that destruction reaches $45–75 billion.

AbbVie can justify paying $8–12 billion for Ventyx to preserve its inflammatory franchise and potentially expand it by positioning VTX3232 as preventive therapy feeding into Skyrizi and Rinvoq for severe cases.

Pfizer: Completing the $10 Billion Investment

Pfizer just spent $10 billion to acquire Metsera and re-enter the obesity market. That investment bought GLP-1 plus amylin agonist assets. Missing from the portfolio: any anti-inflammatory component.

If Lilly launches a triple-benefit combination—weight loss, inflammation reduction, and cardiovascular protection—Pfizer's Metsera portfolio looks incomplete. The inevitable board question: "Why did we pay $10 billion for Phase 2 assets when Lilly owns the complete solution?"

Pfizer must bid $3–6 billion minimum to justify the Metsera strategy. At $15–16 billion total investment across both acquisitions, Pfizer would own GLP-1, amylin, and NLRP3—a differentiated triple combination with peak sales potential of $15–20 billion versus Metsera's standalone $5 billion projection.

Sanofi, Roche, J&J, Novartis: Defensive Imperatives Across the Board

Sanofi has no GLP-1 agonist for obesity but holds a Right of First Negotiation on Ventyx through its $27 million investment. Losing Ventyx means permanent exclusion from the $150 billion obesity market. Winning Ventyx enables partnership with generic semaglutide manufacturers to launch the first affordable inflammation-focused weight loss therapy across emerging markets.

Roche has already invested $7–10 billion building an obesity portfolio through its Carmot and Zealand Pharma acquisitions. CEO Teresa Graham stated publicly: "Our objective is to become one of the top three players in the obesity drug market, and I want to emphasize that I am serious about this ambition." Yet Roche's own NLRP3 program, acquired through Inflazome for €380 million, has stalled without advancing to Phase 3. VTX3232 represents a de-risked path to completing the portfolio.

Johnson & Johnson has no obesity drug in its pipeline but leads in cardiovascular devices and therapeutics. If GLP-1 plus NLRP3 reduces cardiovascular events by preventing upstream inflammation, J&J loses its addressable patient population for stents, ablation equipment, and cardiac interventions. The defensive value of acquiring Ventyx may reach $4–6 billion.

Novartis recently committed $750 million to ProFound Therapeutics for cardiovascular disease targets, signaling strategic focus on under-researched biology. Its own NLRP3 asset, DFV890, acquired through IFM Therapeutics appears to have stalled. Ventyx offers an alternative path.

Why the Metsera Bidding War Sets the Floor, Not the Ceiling

The Metsera precedent establishes what happens when strategic necessity collides with competitive dynamics in the obesity space. The bidding escalated from $4.9 billion to $10 billion in eleven days. Novo Nordisk bid aggressively despite already owning dominant market share. The FTC intervened. Lawsuits were filed.

Ventyx compares favorably to Metsera across nearly every dimension that matters.

Clinical stage: Equal. Both Phase 2.

Indications: Ventyx superior. Metsera targeted obesity alone. Ventyx addresses obesity, cardiovascular disease, Parkinson's, liver disease, and inflammatory disorders.

Peak sales potential: Ventyx superior by a factor of four to eight. Metsera's analyst projections reached $5 billion. VTX3232 combination therapy projections span $20–40 billion given the multi-indication opportunity.

Market timing: Ventyx superior. Metsera entered a pre-generic GLP-1 market. Ventyx arrives as semaglutide goes generic in 40% of the world, dramatically expanding the addressable population for combination therapy.

Competitive threat intensity: Ventyx superior. Metsera faced interest from two bidders. Ventyx threatens the strategic positioning of Novo Nordisk, AbbVie, Pfizer, Sanofi, Roche, J&J, and Novartis simultaneously.

Strategic value: Ventyx superior. Metsera represented offensive market entry. Ventyx represents both offensive opportunity and defensive necessity—bidders must win to avoid losing existing franchises.

The only dimension where Metsera held an advantage was intellectual property clarity. NodThera's recent broad patent filing on NLRP3 plus GLP-1 combinations creates navigation complexity for any acquirer. Yet that complexity arguably increases Ventyx's strategic value: owning VTX3232 provides standing to challenge NodThera's patent and potentially invalidate broad claims through prior art.

If Metsera’s single indication, offensive acquisition justified $10 billion, then Ventyx, with a multi-indication, offensive plus defensive strategic value justifies considerably more.

The Bidding War Projection

Sanofi's Right of First Negotiation creates the initial dynamics. Any offer from Sanofi triggers competitive response from parties who cannot afford to lose the asset. From there, the escalation follows predictable game theory.

Phase 1: Sanofi ROFN Exercise

Sanofi opens at a modest premium over Lilly's $14 offer—perhaps $18 per share, valuing the company at $1.55 billion. The market recognizes immediately that this undervalues the asset given Metsera precedent.

Phase 2: Strategic Bidders Enter

Novo Nordisk bids $35 per share ($3.0 billion)—a signal of serious intent to prevent Lilly monopoly.

AbbVie counters at $40 per share ($3.4 billion)—representing the inflammatory disease defense premium.

Pfizer follows at $45 per share ($3.85 billion)—the price required to complete the Metsera portfolio logic.

Roche enters at $38 per share ($3.25 billion)—finishing the obesity platform it has already invested $7–10 billion to build.

Phase 3: Escalation

As March 2026 approaches, and with it the semaglutide patent expiry that transforms the competitive landscape, strategic urgency intensifies.

Lilly bids $60 per share ($5.1 billion). CEO David Ricks calculates that $5 billion to secure a $30 billion retatrutide franchise represents a 17% insurance premium.

Novo responds at $75 per share ($6.4 billion). CEO Lars Fruergaard Jørgensen recognizes that losing this asset costs $70 billion in market cap; $6.4 billion represents just 9% of that loss.

AbbVie pushes to $85 per share ($7.3 billion). The company is defending a $45 billion inflammatory franchise NPV; $7.3 billion represents a 16% defensive premium.

Phase 4: Resolution

Two outcomes emerge as most probable.

In the first scenario, Novo Nordisk wins at $90–110 per share ($7.7–9.4 billion). The market recognizes Novo overpaid, but acknowledges the company had no choice, as the alternative was permanent strategic disadvantage against Lilly.

In the second scenario, the bidding war approaches or exceeds Metsera pricing at $115–145 per share ($10–12 billion). Multiple bidders refuse to exit. The winner of NLRP3 plus GLP-1 owns the next-generation obesity standard of care. Final bidders, likely Novo and AbbVie, each face existential threats justifying continued escalation.

The most likely outcome falls somewhere in the $100–130 per share range ($8.5–11 billion enterprise value), with Novo Nordisk as the probable winner at roughly $110 per share ($9.4 billion).

Why the Current Valuation Cannot Hold

The central insight is simple: this is not an offensive acquisition valued on risk-adjusted peak sales and discounted cash flows. This is a strategic defense acquisition where bidders pay to prevent catastrophic competitive loss.

The correct valuation framework asks: What is the minimum of offensive NPV and defensive loss prevention?

Offensive NPV for Ventyx reaches $3–7 billion using conventional biotech valuation methods.

Defensive loss prevention runs far higher. Novo faces $50–100 billion in market cap risk. AbbVie faces $30–50 billion in franchise destruction. Pfizer faces obsolescence of a $10 billion investment.

Rational bidders will pay up to 10–20% of their defensive loss to prevent it. That produces a range of $5–20 billion, with the most likely outcome clustering around $10–14 billion, similar to Metsera.

Lilly's $1.2 billion offer sits at the extreme low end of any defensible range. It assumes no competitive bidding. It assumes strategic parties will accept permanent disadvantage rather than pay fair value. It assumes the paradigm shift from weight loss to inflammatory disease treatment will not gain market acceptance.

Those assumptions appear increasingly untenable.

The Timeline and Catalyst Window

The shareholder vote on Lilly's transaction is scheduled for June 2026. Approximately 90% of shares remain uncommitted, meaning any superior proposal triggers fiduciary obligations for Ventyx's board to consider alternatives.

Ventyx expects Phase 2 data from VTX2735 in recurrent pericarditis in late Q1 2026. This readout represents the first human proof of concept for peripheral NLRP3 inhibition in cardiovascular disease. Even base-case success materially de-risks the platform and validates expansion into larger indications.

The combination of a long runway before deal closure, significant catalysts pending, and strategic dynamics favoring competitive bidding suggests the current offer price will not survive contact with reality.

Conclusion

Eli Lilly's bid for Ventyx looks like a reasonable acquisition of a mid-stage biotech when viewed through conventional valuation lenses. Viewed through the lens of strategic competition in the obesity and inflammation space, where the Metsera bidding war just established that Big Pharma will pay $10 billion for Phase 2 assets to prevent competitive disadvantage, the offer appears radically insufficient.

Ventyx controls the most advanced NLRP3 inhibitor platform in clinical development. Its combination data with GLP-1 therapies position it at the center of a paradigm shift from treating obesity as metabolic dysfunction to treating it as chronic inflammatory disease. Every major pharmaceutical company with exposure to obesity, cardiovascular disease, or inflammation faces strategic consequences if a competitor acquires exclusive control.

Markets rarely leave valuation gaps of this magnitude unresolved. The catalyst window extends through mid-2026. The strategic stakes ensure competitive response.

Ventyx may be one of those rare cases where a platform asset is temporarily disguised as a bargain, waiting for strategy, not sentiment to reassert itself.

Disclosure: The author owns shares of Ventyx (VTYX). This article reflects the author's personal views and analysis and is provided for informational purposes only. It does not constitute investment advice or a recommendation to buy or sell any security. Readers should conduct their own due diligence and consider their individual financial circumstances before making any investment decisions.