Section 2: Amylin in Therapeutics

Amylin is a peptide hormone that is co-secreted with insulin by pancreatic beta cells, regulating appetite and glucose levels in the blood.^[1][2] Amylin secretion delays gastric emptying and glucagon secretion, moderating post-meal blood sugar spikes.^[2] The metabolic effects of amylin present meaningful opportunities for therapeutic development, particularly in obesity and Type 2 Diabetes, with viable therapeutic potential in cardiovascular and neurological conditions as well.^[1] While amylin itself is a 37-amino acid peptide, the primary mechanism of therapeutic action involves activating the amylin receptor complex, which is a combined amylin and calcitonin receptor whose amylin component is comprised of three distinct receptor activity-modifying proteins: AMYR1, AMYR2, and AMYR3, each conferring distinct pharmacological properties.^[1] Different therapies in development selectively target different components of this receptor complex. Combining amylin-based therapies with GLP-1 or GIP receptor agonists leverages the weight loss efficacy of both mechanisms while providing the added benefits of amylin targeting, notably less reduction in lean mass and improved tolerability.^[3][4]

Common Amylin Therapy Molecule Types

• Synthetic amylin analogue: Peptide molecules structurally similar to amylin, modified to improve biological properties such as pharmacokinetics / pharmacodynamics, receptor selectivity, and half-life. The majority of assets in this report fall into this category.
• Small molecule amylin agonist: A non-peptide molecule capable of binding to and activating the amylin receptor complex without structural similarity to amylin itself. ACCG-2671 (Structure Therapeutics) is included in the report as an oral small molecule DACRA in clinical development.
• Synthetic co-analogue: A single peptide molecule engineered to exhibit receptor activity at both the amylin and another key hormone receptor, most commonly GLP-1. Zenagamtide (Novo Nordisk) is the leading example of this molecule type in the pipeline.

Common Amylin Therapy Molecular Targeting Strategies

• Dual amylin calcitonin receptor agonist (DACRA): Targets both the amylin and calcitonin components of the receptor complex. Joint activation is thought to produce longer-lasting receptor engagement and greater therapeutic effect, particularly greater weight loss.
• Selective amylin receptor agonist (SARA): Targets only the amylin component of the receptor complex, or a specific amylin receptor subtype (e.g., AMY1R only). This approach may offer advantages in GI tolerability and lean mass preservation by avoiding calcitonin receptor co-activation.

Common Amylin Therapy Treatment Regimen Strategies

• Monotherapy: Many earlier-stage trials evaluate amylin receptor agonists as standalone therapies. The biological rationale, however, increasingly points to greater treatment effect in obesity when amylin is combined with GLP-1s or similar agents.
• Combination therapy: Pairing an amylin receptor agonist with a GLP-1 or GIP receptor agonist has emerged as the dominant paradigm in later-stage clinical development, underlying the most promising treatment regimens in the pipeline.

Section 3: Notable Amylin Pipeline Assets

The table below summarizes the ten amylin-targeting assets profiled in this report, mostly comprised of phase 2 and 3 clinical stage assets as well as some promising preclinical and phase 1 therapies.

1. CagriSema (Novo Nordisk)

Drug Name(s): CagriSema (cagrilintide + semaglutide)
Molecule Type: Cagrilintide: amylin analogue; Semaglutide: GLP-1 analogue
Receptor Target(s): Cagrilintide: amylin and calcitonin receptors^[5]; Semaglutide: GLP-1 receptor^[6]
Therapeutic Strategy: Dual GLP-1 and amylin receptor agonism via fixed-dose combination regimen
Route of Administration: Subcutaneous injectable (both components)^[7]
Lead Target Indication: Obesity^[7]
Sponsor: Novo Nordisk
Sponsor Country: Denmark
Trial Name / NCT ID: REDEFINE 1 (NCT05567796)
Trial Phase: Phase 3 (Completed, NDA Filed)

Trial Progress & Key Data

The REDEFINE 1 trial read out in June 2025, demonstrating a 22.7% mean weight reduction in adults with overweight or obesity.^[8] Weight loss was predominantly from fat mass (~36%) rather than lean mass (~14%), a healthier long-term outcome for patients.^[8] Based on these results, Novo Nordisk submitted an NDA in December 2025, with FDA review and a potential regulatory decision expected in 2026.^[9]

Beyond REDEFINE 1, a broad clinical program is underway evaluating CagriSema across multiple patient populations and disease settings:

• REDEFINE-2: Obesity with Type 2 Diabetes comorbidity^[10]
• REDEFINE-3: Cardiovascular disease^[11]
• REIMAGINE 1: Type 2 Diabetes^[12]
• Additional REDEFINE and REIMAGINE trials are testing CagriSema against various treatment regimens and patient subgroups across obesity and T2D

Competitive Outlook

• Combining the two therapies into a single injection, as opposed to two separate injections, provides added benefit for patient experience and treatment adherence, not to mention added weight loss effect from receiving both a GLP-1 and amylin-based therapy.
• A weight reduction of over 20% with weight loss predominantly from fat mass (~36%) as opposed to lean mass (~14%) provides a meaningful treatment effect with favorable outcomes in terms of preserved lean mass.^[8]
• Targeting of amylin and calcitonin receptors jointly is thought to lead to longer receptor activation and greater therapeutic effect, such as greater weight loss.^[13]

2. Cagrilintide (Novo Nordisk)

Drug Name(s): Cagrilintide
Molecule Type: Amylin analogue
Receptor Target(s): Amylin and calcitonin receptors (DACRA)^[5]
Therapeutic Strategy: Amylin receptor agonist monotherapy
Route of Administration: Subcutaneous injectable
Lead Target Indication: Obesity^[14]
Sponsor: Novo Nordisk
Sponsor Country: Denmark
Trial Name / NCT ID: RENEW 1 (NCT07220642)^[14]
Trial Phase: Phase 3

Trial Progress & Key Data

RENEW 1 has not yet read out primary data, with primary study completion expected in May 2027. Interim readouts are possible but Novo Nordisk does not routinely publish interim results. Phase 3 data on cagrilintide monotherapy derived from the cagrilintide arm of the REDEFINE 1 trial became available in September 2025, providing the most current benchmark for the monotherapy program.^[15]

Competitive Outlook

• With around 12% body weight reduction using the monotherapy, the therapeutic argument is not as strong as Novo's CagriSema strategy and other combination treatments.
• Targeting of amylin and calcitonin receptors jointly is thought to lead to longer receptor activation and greater therapeutic effect, such as greater weight loss.^[13]

3. Zenagamtide (Novo Nordisk)

Drug Name(s): Zenagamtide, amycretin
Molecule Type: Unimolecular amylin and GLP-1 co-analogue^[16]
Receptor Target(s): Amylin, calcitonin, and GLP-1 receptors^[17]
Therapeutic Strategy: Amylin and GLP-1 receptor dual-agonist monotherapy
Route of Administration: Subcutaneous injectable; oral formulation also in development^[18]
Lead Target Indication: Obesity, Type 2 Diabetes^[18]
Sponsor: Novo Nordisk
Sponsor Country: Denmark
Trial Name / NCT ID: NCT07400107
Trial Phase: Phase 3

Trial Progress & Key Data

The Phase 3 trial (NCT07400107) evaluates zenagamtide across both obesity and Type 2 Diabetes and was initiated in May 2026, with an estimated primary completion date of December 2028.^[19] The pivotal data supporting the Phase 3 decision comes from Phase 1b/2a results demonstrating up to ~24% weight loss at the highest administered dose.^[20]

Phase 2 results presented at the ADA 2026 conference showcased significant A1C reductions alongside 14.6% weight loss after 36 weeks in a large majority of patients, further supporting the dual-indication Phase 3 strategy.^[21]

Competitive Outlook

• A single therapy that activates amylin, calcitonin, and GLP-1 receptors combines greater treatment effect with ease of regimen and drug administration for the patient.
• The oral formulation would further enhance the drug's convenience for patients.
• Targeting of amylin and calcitonin receptors jointly is thought to lead to longer receptor activation and greater therapeutic effect, such as greater weight loss.^[13]

4. Petrelintide (Zealand Pharma / Roche)

Drug Name(s): Petrelintide, ZP8396
Molecule Type: Amylin analogue
Receptor Target(s): Amylin and calcitonin receptors (DACRA)^[22]
Therapeutic Strategy: Amylin receptor agonist monotherapy
Route of Administration: Subcutaneous injectable
Lead Target Indication: Obesity (with hypertension and/or dyslipidemia comorbidities)
Sponsor: Zealand Pharma, Roche
Sponsor Country: Denmark, Switzerland
Trial Name / NCT ID: ZUPREME-1 (NCT06662539)^[23]
Trial Phase: Phase 2 (Completed)

Trial Progress & Key Data

Topline data from ZUPREME-1 demonstrated a statistically significant 10.7% mean body weight reduction at week 42 versus 1.7% with placebo in the best-performing intervention arm, with the primary endpoint met.^[24] Based on these results, Zealand Pharma and Roche announced plans to advance petrelintide to Phase 3, with the trial expected to begin in H2 of 2026.^[25]

Competitive Outlook

• Body weight reduction of ~11% is in line and competitive with Novo's cagrilintide, and in much the same manner inferior to the weight loss effects of amylin and GLP-1 combination regimens.
• Targeting of amylin and calcitonin receptors jointly is thought to lead to longer receptor activation and greater therapeutic effect, such as greater weight loss.^[13]

5. Petrelintide + Enicepatide (Zealand Pharma / Roche)

Drug Name(s): Petrelintide, ZP8396 + Enicepatide, CT-388
Molecule Type: Petrelintide: amylin analogue; Enicepatide: unimolecular GLP-1 and GIP analogue^[26]
Receptor Target(s): Petrelintide: amylin and calcitonin receptors^[22]; Enicepatide: GLP-1 and GIP receptors^[27]
Therapeutic Strategy: Amylin and GLP-1/GIP targeting combination regimen
Route of Administration: Subcutaneous injectable (both components)
Lead Target Indication: Obesity, followed by T2D^[28]
Sponsor: Zealand Pharma, Roche
Sponsor Country: Denmark, Switzerland
Trial Name / NCT ID: ZYNERGY (NCT07589686)^[29]
Trial Phase: Phase 2 (Initiating)

Trial Progress & Key Data

The ZYNERGY Phase 2 trial has not yet been initiated, with kickoff expected in mid-2026.^[29] The clinical rationale for this combination is supported by separate monotherapy Phase 2 data across both assets:

• ZUPREME-1 (petrelintide, obesity): Statistically significant 10.7% mean body weight reduction at week 42 versus 1.7% with placebo; primary endpoint met.^[24]
• ZUPREME-2 (petrelintide, obesity + T2D): Phase 2 trial ongoing; no readout yet, with data expected mid-2026.^[24][30]
• CT-388-103 (enicepatide, obesity): Phase 2 topline results showed statistically significant weight loss of 22.5% at the highest tested dose.^[31][32]

Competitive Outlook

• While weight loss data for each therapy in this regimen exists independently, whether there will be an additive effect when combined remains unproven until a data readout from ZYNERGY.
• Effects across amylin, calcitonin, GLP-1, and GIP receptors could provide a synergistic increase in treatment effect, but also increase the risk of treatment tolerability issues.

6. AZD6234 (AstraZeneca)

Drug Name(s): AZD6234
Molecule Type: Amylin analogue peptide^[33]
Receptor Target(s): Amylin receptor (selective; no calcitonin receptor activation)^[34]
Therapeutic Strategy: Selective amylin receptor agonist (SARA) monotherapy; also being evaluated in combination with AZD9550, a GLP-1R/glucagon dual agonist^[35]
Route of Administration: Subcutaneous injectable^[36]
Lead Target Indication: Obesity^[35]
Sponsor: AstraZeneca
Sponsor Country: United Kingdom
Trial Name / NCT ID: APRICUS (NCT06595238)^[37]
Trial Phase: Phase 2

Trial Progress & Key Data

Primary data from APRICUS is expected imminently; AstraZeneca has acknowledged awareness of the results but has not yet released them publicly.^[38] Two additional Phase 2 trials are also approaching data readout:

• ARAY (NCT06851858): Evaluating AZD6234 in patients with obesity and Type 2 Diabetes who are already on a GLP-1 regimen. Data expected soon given the trial's primary completion timeline.^[36]
• ASCEND (NCT06862791): Evaluating AZD6234 in combination with AZD9550, a GLP-1R/glucagon dual agonist, in obesity. Data readout on a similar timeline to ARAY.^[39]

Competitive Outlook

• Competitive outlook is difficult to form prior to Phase 2 data readouts from APRICUS, ARAY, or ASCEND.
• Selective targeting of the amylin receptor while avoiding calcitonin has the potential upside of improved GI tolerability, avoiding calcium-lowering effects with implications for bone biology, and greater lean mass preservation. These effects are still being investigated and will need to be robustly captured in these trials; however, primary and secondary endpoints for all three trials do not appear to include such endpoints, leaving a potential competitive advantage on the table or delay of measuring these effects until Phase 3 trials commence.

7. ACCG-2671 (Structure Therapeutics)

Drug Name(s): ACCG-2671
Molecule Type: Oral small molecule^[40]
Receptor Target(s): Amylin and calcitonin receptors (DACRA)^[41]
Therapeutic Strategy: Dual amylin and calcitonin receptor agonist monotherapy
Route of Administration: Oral
Lead Target Indication: Obesity^[42]
Sponsor: Structure Therapeutics
Sponsor Country: United States
Trial Name / NCT ID: Phase 1 trial (details not yet publicly registered)
Trial Phase: Phase 1

Trial Progress & Key Data

Phase 1 data readout is anticipated in H2 2026. Structure Therapeutics also has a second oral small molecule DACRA, ACCG-3535, in IND-enabling and preclinical development.^[42]

Competitive Outlook

• Targeting of amylin and calcitonin receptors jointly is thought to lead to longer receptor activation and greater therapeutic effect, such as greater weight loss.^[13]
• The asset is too early in development to assess clinical efficacy and meaningful competitive advantages.

8. VRB-103 (Verdiva Bio)

Drug Name(s): VRB-103
Molecule Type: Amylin analogue
Receptor Target(s): Amylin receptor (selective; SARA)^[43]
Therapeutic Strategy: Selective amylin receptor agonist (SARA) monotherapy; also being evaluated in combination with VRB-101, a GLP-1 analogue^[44]
Route of Administration: Oral
Lead Target Indication: Obesity
Sponsor: Verdiva Bio
Sponsor Country: United Kingdom
Trial Name / NCT ID: NCT07628127^[45]
Trial Phase: Phase 1 (Initiating)

Trial Progress & Key Data

The Phase 1 trial is expected to commence in July 2026, evaluating both VRB-103 monotherapy and VRB-103 in combination with VRB-101.^[45] The most recent data comes from a preclinical study presented at ADA 2026 demonstrating greater receptor selectivity compared to eloralintide (Eli Lilly) and cagrilintide (Novo Nordisk) in head-to-head preclinical assessment.^[46]

Verdiva Bio has a broader amylin-targeting preclinical pipeline: VRB-104, a unimolecular GLP-1 plus amylin co-agonist analogous to zenagamtide's molecular strategy, and VRB-102, a peptide amylin analogue, have both demonstrated promising preclinical results.^[46][44]

Competitive Outlook

• Other than Novo Nordisk's zenagamtide, VRB-103 appears to be one of the only other amylin analogues that has been successfully developed as an oral formulation, which presents a unique route of administration while retaining the advantages of amylin analogue-based therapies.
• Verdiva's multiple amylin-based pipeline assets in development (VRB-103, VRB-104, and VRB-102) provide distinct molecular strategies to achieve competitive clinical efficacy outcomes.
• Combination with GLP-1 analogue VRB-101 is likely to enhance weight loss treatment effect.

9. Eloralintide (Eli Lilly)

Drug Name(s): Eloralintide, LY3841136
Molecule Type: Amylin analogue peptide^[47]
Receptor Target(s): AMY1R (specific amylin-1 receptor subtype)
Therapeutic Strategy: Selective AMY1R agonist monotherapy; also being tested in combination with tirzepatide (GLP-1R/GIPR dual agonist)
Route of Administration: Subcutaneous injectable
Lead Target Indication: Obesity
Sponsor: Eli Lilly
Sponsor Country: United States
Trial Name / NCT ID: ENLIGHTEN-1 (NCT07321886)^[48]
Trial Phase: Phase 3

Trial Progress & Key Data

ENLIGHTEN-1 has recently been initiated and has not yet read out. The most recent data comes from the Phase 2 trial in obesity (NCT06230523), which demonstrated mean weight reductions ranging from 9.5% to 20.1% across treatment arms versus 0.4% in the placebo arm, with the primary endpoint met in all treatment arms.^[49][50]

Eli Lilly is advancing eloralintide across multiple Phase 3 programs in parallel:

• ENLIGHTEN-1 (NCT07321886): Obesity^[48]
• Phase 3, obesity + T2D (NCT07282600)^[51]
• Phase 3 in obstructive sleep apnea and osteoarthritis^[52]
• Eloralintide + tirzepatide combination Phase 3 (Phase 2 NCT06603571 for the same combination regimen is near completion)^[50][52]

Competitive Outlook

• Mean weight loss of 9% - 20% from eloralintide alone is highly competitive, as many other amylin-based monotherapies achieve weight loss around the 10% mark.
• Combining this level of demonstrated efficacy with tirzepatide could produce a potential leader on the clinical efficacy front within the amylin and GLP-1 combination regimen treatment landscape.
• Selective targeting of AMY1R in particular may offer gastrointestinal tolerability benefits, as evidenced by preclinical and early-stage clinical data.^[47]

10. VK3019 (Viking Therapeutics)

Drug Name(s): VK3019
Molecule Type: Likely a peptide amylin analogue^[53]
Receptor Target(s): Amylin and calcitonin receptors (DACRA)
Therapeutic Strategy: Amylin receptor agonist monotherapy, although Viking has indicated intent to further develop in combination with GLP-1 and GLP-1/GIP agonists^[54]
Route of Administration: TBD
Lead Target Indication: TBD
Sponsor: Viking Therapeutics
Sponsor Country: United States
Trial Name / NCT ID: TBD
Trial Phase: Phase 1 (Initiating)

Trial Progress & Key Data

Phase 1 initiation is expected in Q2 2026.^[55] Preclinical data released in June 2024 demonstrated weight loss of up to 8% in rats, with results described as comparable to cagrilintide in the preclinical setting.^[53]

Competitive Outlook

• While it is too early to indicate effect in humans, preclinical weight loss data is slightly below or in line with results of other amylin-based monotherapies.
• Phase 1 and, especially, Phase 2 trials must commence and read out before any legitimate claims about clinical efficacy or VK3019's competitive profile can be made.
• Targeting of amylin and calcitonin receptors jointly is thought to lead to longer receptor activation and greater therapeutic effect / weight loss.^[13]