What changed, and when

Halozyme and Skye announced a non-exclusive global collaboration and license on January 5, 2026, to evaluate nimacimab co-formulated with ENHANZE for obesity, with mid-single-digit royalties to Halozyme and a planned Phase 2b start in mid-2026. (PR Newswire release). Independent trade coverage confirms deal contours and Phase 2b timing. (Contract Pharma, Investing.com brief).

60-second thesis frame

This pact gives Skye an industrialized path to higher subcutaneous nimacimab doses and larger injection volumes, potentially enabling practical monotherapy or GLP-1 combinations if efficacy tightens in Phase 2b. ENHANZE, based on rHuPH20, is a validated route to rapid, higher-volume SC delivery, recently used in an FDA-approved subcutaneous amivantamab formulation, which supports the platform’s credibility for large biologics (Halozyme ENHANZE overview, FDA approval page for Rybrevant Faspro). Nimacimab targets peripheral CB1 with a negative allosteric mechanism, a differentiated approach that aims to preserve CNS safety while affecting metabolic pathways, but Phase 2a topline showed mixed signals, with monotherapy underwhelming and combo signals more encouraging, so Phase 2b dose, exposure, and combo design are pivotal (Skye Phase 2a topline, ClinicalTrialsArena coverage, ClinicalTrials.gov NCT06577090).

The seven diligence questions

Clinical

• Does higher-dose nimacimab, enabled by ENHANZE, achieve clinically meaningful, placebo-adjusted weight loss at 26–52 weeks as monotherapy, and what is the effect in combination with GLP-1 agents such as semaglutide in a pre-specified hierarchy? (ClinicalTrials.gov NCT06577090, Skye Phase 2a topline)
• Is peripheral CB1 blockade delivering metabolic effects without CNS liabilities seen with prior central CB1 antagonists, and are GI or injection-site AEs additive with GLP-1s at higher volumes? (Lancet Diabetes & Endocrinology comment on peripheral CB1, PMC review of rHuPH20/SC delivery)

Payer or Access

• If efficacy is additive to GLP-1s, will payers accept dual therapy for obesity or step-edit to GLP-1 failure first, and how will codes and prior auth evolve for combination regimens in 2026–2027? (Analogue policies often reference existing GLP-1 criteria; confirm local PBM policies)
• What price and dosing cadence are feasible for a large-volume SC biologic in obesity, and can ENHANZE support at-home administration to lower site-of-care costs? (Halozyme ENHANZE overview)

Ops or Adoption

• Can co-formulation with ENHANZE reliably deliver higher volumes through practical devices and patient-acceptable injection times in obesity trials and routine use, and what is device strategy if volumes remain high? (Halozyme ENHANZE overview)

Competitive

• Against rapid entrants and incumbents in obesity and combo regimens, where could nimacimab fit, especially if efficacy is moderate but tolerability or durability off-drug is better than incretins? Independent coverage flagged mixed Phase 2a signals that heighten design risk for Phase 2b. (ClinicalTrialsArena coverage)

Team or Cap table

• Does Skye’s runway and partner network support a global Phase 2b with GLP-1 combinations and device workstreams through readout, after pivoting from ophthalmology in 2024, and are milestone obligations to Halozyme manageable under different success scenarios? (Reuters on 2024 pivot, Skye–Halozyme IR post)

Red flags

• Mixed Phase 2a readout with monotherapy underperformance versus expectations, raising bar for Phase 2b dose–exposure and combo effect size. (Skye Phase 2a topline, ClinicalTrialsArena coverage)
• Execution complexity, co-formulation and device requirements for higher-volume SC dosing in an obesity population where convenience and adherence drive persistence. (Halozyme ENHANZE overview)
• Competitive intensity in obesity combinations, with rapid label and payer dynamics that may constrain uptake without clear differentiation. (General market context, cross-check with payer analogues)

Next catalyst

Skye guides to initiate a Phase 2b obesity study of nimacimab with ENHANZE in mid-2026, including a GLP-1 combination cohort, with protocol details expected in filings or conference updates. (PR Newswire release, Skye–Halozyme IR post)

FAQ

• What exactly changed by Halozyme and Skye’s collaboration news on nimacimab co-formulated with ENHANZE for obesity, and why does it matter for the obesity market?
  The parties signed a non-exclusive deal in December 2025 enabling ENHANZE to support higher-volume SC dosing of nimacimab, potentially facilitating dose ranging and GLP-1 combinations for obesity. (PR Newswire release, Contract Pharma)
• What is the regulatory path after the Halozyme – Skye announcement, and what are the next formal steps in the US, UK, and EU?
  The near-term step is a Phase 2b start to confirm dose, exposure, and combination effects; any future filings would depend on robust Phase 3 outcomes, with no expedited US or EU designations disclosed. ENHANZE’s platform validation is supported by FDA approval of subcutaneous amivantamab with hyaluronidase-lpuj, but this does not predict nimacimab outcomes. (FDA approval page)
• Which endpoints in CBeyond Phase 2a drove the narrative in the October 6, 2025 topline news, and how meaningful was the effect size?
  Company communications indicated monotherapy underperformed while combination with a GLP-1 showed more promising signals, creating uncertainty around magnitude and durability. Independent coverage highlighted the disappointment in monotherapy, which raises the Phase 2b bar. (Skye Phase 2a topline, ClinicalTrialsArena coverage)
• What safety issues matter post–Halozyme-Skye collaboration news, and do they change real-world use?
  The core question is whether peripheral CB1 inhibition avoids CNS adverse effects that doomed prior central CB1 drugs, while maintaining tolerability when combined with GLP-1s at higher SC volumes. Peripheral CB1 rationale is supported in recent literature, but clinical confirmation in obesity is pending. (Lancet Diabetes & Endocrinology comment)
• How will major US payers treat access after the January 5, 2026 Halozyme-Skye news, including prior auth or step edits, and are codes available?
  Payers will likely anchor on GLP-1 criteria and real-world outcomes, reserving combination reimbursement for clear additive benefit or special populations; coding would follow standard drug and administration pathways if approved. Public insurer policy signals for this novel combo approach are not yet published and should be monitored. (Policy analogues required; no direct payer policies available yet).

Publisher / Disclosure

Publisher: LucidQuest Ventures Ltd. Produced: 05 Jan 2026, 08:00 London. Purpose: general and impersonal information. Not investment research or advice, no offer or solicitation, no suitability assessment. UK: directed at investment professionals under Article 19(5) and certain high-net-worth entities under Article 49(2)(a)–(d) of the Financial Promotion Order 2005. Others should not act on this. Sources and accuracy: public sources believed reliable, provided “as is,” may change without notice. No duty to update. Past performance is not reliable. Forward-looking statements carry risks. Methodology: questions-first framework using public sources. No conflicts. Authors do not hold positions unless stated. © 2026 LucidQuest Ventures Ltd.

Entities / Keywords

Halozyme; Skye Bioscience; ENHANZE; rHuPH20; nimacimab; CB1; peripheral CB1 blockade; GLP-1; semaglutide; Wegovy; Rybrevant Faspro; amivantamab and hyaluronidase-lpuj; FDA; EMA; MHRA; obesity; CBeyond; NCT06577090; Phase 2a; Phase 2b; subcutaneous large-volume injection; device strategy; payer prior authorization; PBMs; royalties; milestones; combination therapy; durability of weight loss; CNS safety; ClinicalTrials.gov; Reuters; Contract Pharma.