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Item 1. Business

2026-03-10 compared with 2025-03-20 · 134 added, 69 removed, 438 unchanged (32% of the section changed)

Skye Bioscience, Inc.

is a clinical stage biotechnology company pioneering next-generation molecules that modulate G-protein-coupled receptors ("GPCRs") to treat obesity, overweight, and related conditions.

is a clinical-stage biotechnology company pioneering next-generation molecules that modulate G-protein-coupled receptors ("GPCRs") to treat obesity, overweight, and metabolic disorders.

Our lead candidate, nimacimab, is a peripherally restricted negative allosteric modulating antibody targeting cannabinoid receptor 1 ("CB1")—a key GPCR involved in metabolic regulation.

We are conducting CBeyond TM , a Phase 2a proof-of-concept trial of nimacimab administered as a subcutaneous injectable for the treatment of obesity and overweight in the United States.

The CBeyond TM study is also assessing the combination of nimacimab and a GLP-1 receptor agonist.

We anticipate providing a top-line readout from the CBeyond™ study late in the third quarter or early in the fourth quarter of 2025, enabling a comprehensive view of nimacimab’s safety and efficacy profile.

Except where the context indicates otherwise, references to "we," "us," "our," "Skye" or the" Company" refer to the company and its subsidiaries.

Beyond nimacimab, our strategy is to develop and implement proprietary methods and platform technologies aimed at advancing a broad, scalable, and combinable portfolio of GPCR-based therapeutics to treat obesity, overweight and related conditions.

Our goal is to address not only the limitations of approved therapies, but also many of the anticipated challenges posed by next-generation treatments.

Through this anticipated future pipeline, we will remain committed to transforming metabolic health and delivering breakthrough treatments for high-burden, life-threatening conditions.

We believe there is a growing demand for therapies that offer improved safety, efficacy, tolerability, quality of life and long-term health outcomes while addressing the limitations of currently approved treatments.

Our objective is to drive innovation in the treatment landscape for obesity, overweight and metabolic disorders by developing first-in-class therapies that meet significant unmet medical needs globally.

Our objective is to drive innovation in the treatment landscape for obesity, overweight and metabolic disorders by developing potential first-in-class therapies that meet significant unmet medical needs globally.

Key elements of our strategy include:

• Advancing nimacimab through clinical development with an initial focus on completing the CBeyond Phase 2a study for the treatment of patients with obesity and overweight and evaluating its potential as a standalone, second-line or combination therapy.

• Advancing nimacimab through clinical development for the treatment of patients with obesity and overweight as a combination therapy and evaluating its potential as a standalone or second-line therapy.

• Expanding the clinical utility of nimacimab by exploring additional metabolic indications where inflammation and fibrosis c ontribute to disease progression, utilizing translational models to identify new therapeutic applications .

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• Expanding our pipeline through in-licensing or acquisitions of complementary metabolic health technologies and product candidates that target GPCRs and align with our strategic vision.

The status of our development pipeline is as follows:

Our Product Candidate

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(“Bird Rock”), a privately held, clinical-stage biotechnology company, in August 2023.

Through this transaction, we acquired nimacimab, a humanized IgG4 negative allosteric modulating ("NAM") antibody that specifically binds to the CB1 receptor with no cross-reactivity to other GPCRs, including cannabinoid receptor 2 ("CB2") .

Nimacimab was originally evaluated in a Phase 1 clinical study for nonalcoholic fatty liver disease related to a different development strategy.

We are now conducting a Phase 2a proof-of-concept trial of nimacimab in people with overweight and obesity and expect to report a top-line readout late in the third quarter or early in the fourth quarter of 2025.

To obtain 52 weeks of treatment data, the CBeyond trial will be extended to provide a longer-term assessment of safety, tolerability and efficacy.

The protocol extension will provide for continued assessment of both the nimacimab monotherapy (primary endpoint) and the nimacimab/GLP-1 combination cohort (exploratory endpoint).These results will represent the first in-human clinical data for nimacimab in the treatment of obesity.

Through this transaction, we acquired nimacimab, a humanized IgG4 negative allosteric modulating ("NAM") antibody that specifically binds to the CB1 receptor with no cross-reactivity to certain other GPCRs, including cannabinoid receptor 2 ("CB2") .

Unmet Need and Market Opportunity

Global obesity rates have been rising dramatically, affecting more than one billion people worldwide (approximately 650 million adults).

Obesity and overweight are complex diseases characterized by excess and chronic inflammation of adipose tissues, and it results from a chronic energy surplus in which the body’s energy intake exceeds its energy expenditure.

Obesity is a complex, heterogeneous, chronic, and progressive disease, which substantially affects health, quality of life and mortality.

"Obesity" and "severe obesity" are defined by a body mass index ("BMI") of greater than 30 and 40 kg/m2, respectively, with abnormal or excessive fat accumulation.

"Overweight" is defined by a BMI of greater than 25 kg/m2.

Obesity and overweight states are characterized by a chronic energy surplus in which the body’s energy intake exceeds its energy expenditure and are often associated with excess and chronic inflammation of adipose and other tissues.

Other stressors and environmental factors contribute to this chronic imbalance.

Today, obesity is the fifth-leading risk factor cited by the World Health Organization ("WHO") for contributing as a primary cause of death globally.

Based on estimates by the WHO, globally, obesity affected more than 890 million adults as of 2022, and we believe it has continued to increase in prevalence worldwide since the WHO declared a global obesity epidemic in 1997.

In addition, the WHO estimates that 2.5 billion adults were overweight as of 2022.

Current estimates by the World Obesity Atlas suggest that 54% of the global population will be overweight or obese by 2035, compared to 46% in 2025.

In addition, it is estimated that 39% of, or 770 million, children between the ages of five and nineteen years of age will be overweight or obese by 2035 compared to 28% of, or 550 million, such children in 2025.

Based on several analyst estimates, we believe this deeply rooted global health crisis could represent a total addressable market of more than $100 billion annually by 2030.

Previous treatments for obesity have been limited by safety concerns and insufficient efficacy, which we believe hindered their success.

However, incretin-based therapeutics has shown significant weight loss and positive cardiovascular effects in clinical studies.

GLP-1 receptor agonists ("GLP-1") have been effective in reducing overall body weight, but this weight loss also includes, on average, an estimated 25-40% loss of lean muscle mass.

However, incretin-based therapeutics have shown significant weight loss and positive cardiovascular effects in clinical studies.

While glucagon-like peptide-1 ("GLP-1") receptor agonists have been effective in reducing overall body weight, this weight loss also includes, on average, an estimated 25-40% loss of lean muscle mass.

Patients using GLP-1 therapies also face tolerability issues, particularly gastrointestinal discomfort, which can affect the duration of treatment and lead to high rates of discontinuation.

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Despite the remarkable efficacy and commercial success of GLP-1 therapies, we believe there is still potential to improve the quality and sustainability of weight loss regimens, as well as, help patients who can not tolerate or do not respond to GLP-1 therapies.

We believe the combination of non-incretin mechanisms with incretin therapies like GLP-1s could improve outcomes compared to solely using GLP-1 therapies.

We believe the combination of non-incretin mechanisms, such as nimacimab, with incretin therapies like GLP-1s could improve outcomes compared to solely using incretin therapies.

Alternatively, we believe a non-incretin mechanism could be used as a follow-up to standard GLP-1 treatments or as an alternative for specific patient groups with obesity and overweight.

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Activation of CB1 promotes fat accumulation and disrupts mitochondrial function in obesity models, whereas inhibiting CB1 enhances mitochondrial biogenesis.

This metabolic adjustment results in weight loss primarily through heightened energy expenditure, increased lipolysis, and fatty acid oxidation processes, particularly in brown adipose tissue.

This metabolic adjustment results in weight loss through heightened energy expenditure, increased lipolysis, and fatty acid oxidation processes, particularly in brown adipose tissue.

CB1 Inhibition:

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It has been previously demonstrated that inhibiting the CB1 receptor can significantly reduce weight in patients with obesity.

In 2006, Sanofi developed a small molecule CB1 inverse agonist called rimonabant, which demonstrated 10% weight loss after one year.

In 2006, Sanofi (formerly Sanofi-Aventis) developed a small molecule CB1 inverse agonist called rimonabant, which demonstrated 10% or greater weight loss after one year, in 25.2% of patients receiving 20 mg of rimonabant.

Despite being approved by the European Medicines Agency, the drug was soon taken off the market due to severe adverse neuropsychiatric side effects, including suicidal ideation.

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Ultimately it was determined that rimonabant, a small molecule, readily entered the brain, resulting in severe adverse neuropsychiatric side effects.

A new generation of small molecule CB1 inhibitors are being developed with the aim of achieving further peripheral restriction.

Small molecule-based CB1 inverse agonists have been modified to discourage distribution in the CNS and brain by increasing the polarity of surface residues, which also impacts membranous trafficking and bioavailability.

A new generation of small molecule CB1 inhibitors are being developed with the aim of minimizing inhibition of CB1 receptors in the brain and maximizing exposure in the peripheral tissues.

These new generation small molecule CB1 inverse agonists have been modified to discourage distribution in the CNS and brain by increasing the polarity of surface residues, which also impacts membranous trafficking and bioavailability.

While these altered small molecules yield notable reductions in CNS distribution relative to non-biased small molecules such as rimonabant, its presence and significant CB1 occupancy in the brain has still been noted in chronic preclinical and clinical settings.

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We believe that the safest and most effective way to inhibit CB1 is with a large-molecule approach to potentially eliminate safety concerns from the molecule penetrating the blood-brain barrier.

We believe nimacimab, as a large molecule, has the potential to mitigate safety concerns associated with the CB1 class and may achieve similar or more favorable efficacy than other therapies in the CB1 class due to our ability to administer higher doses of nimacimab, without significant concentrations of nimacimab penetrating the blood-brain barrier.

We believe nimacimab, as a large molecule, has the potential to mitigate safety concerns associated with the CB1 class due to our ability to administer higher doses of nimacimab, without significant concentrations of nimacimab penetrating the blood-brain barrier.

Nimacimab Product Differentiation

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For example, based on clinical trial data for semaglutide, a GLP-1 agonist, on average 25-40% of the weight loss results from the loss of lean mass (which can include both muscle and bone).

In addition, up to 70% of patients experience gastrointestinal ("GI") side effects with semaglutide including nausea, vomiting and diarrhea, which can lead to discontinuation of treatment in some cases.

In addition, up to 70% of patients experience gastrointestinal ("GI") side effects with semaglutide including nausea, vomiting, constipation and diarrhea, which can lead to discontinuation of treatment in some cases.

We believe nimacimab stands apart from GLP-1s and other incretin-based weight loss therapies because its primary mechanism goes beyond suppression of food intake.

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Enhanced Selectivity and Safety - As an antibody, nimacimab exhibits high specificity for CB1, reducing the risk of off-target toxicity—a critical factor given the historical safety concerns with CB1 inhibition.

Our Phase 1 study established the potential for nimacimab’s favorable safety profile, with no observed neuropsychiatric adverse effects and excellent GI tolerability, a key differentiation from previous CB1-targeting drugs.

Our Phase 1 and Phase 2a studies established the potential for nimacimab’s favorable safety profile, with no observed neuropsychiatric adverse effects and excellent GI tolerability, a key differentiation from previous CB1-targeting drugs.

Negative Allosteric Modulation - Nimacimab functions as a negative allosteric modulator of CB1, which means it binds to a distinct area of CB1 'away' from the receptor’s primary active site (the orthosteric site) and thus inhibits CB1 activity without any competition from the endogenous ligands (endocannabinoids).

This noncompetitive mode of action is distinct from small-molecule inhibitors, which target CB1 receptor’s orthosteric site and require successful competition with endocannabinoids for receptor occupancy to inhibit CB1 signaling.

This can become critical as CB1 signaling is often overactive in metabolic diseases, and direct competition with an inverse agonist may be insufficient in tissues with excessive CB1 activity.

In such disease states, where both CB1 receptor density and endocannabinoid levels are elevated, orthosteric small molecules must outcompete high concentrations of endocannabinoids, which can negatively impact their Pharmacokinetic ("PK") profile and ultimately limit their efficacy.

We believe this noncompetitive mode of action is distinct from small-molecule inhibitors, which target CB1 receptor’s orthosteric site and require successful competition with endocannabinoids for receptor occupancy to inhibit CB1 signaling.

We believe this can become critical as CB1 signaling is often overactive in metabolic diseases, and direct competition with an inhibitor that binds at the orthosteric site and competes with endocannabinoids for binding to the receptor may be insufficient in tissues with excessive CB1 activity.

In such disease states, where both CB1 receptor density and endocannabinoid levels are elevated, orthosteric small molecules must outcompete high concentrations of endocannabinoids, which can negatively impact their Pharmacodynamic ("PD") profile and ultimately limit their efficacy.

Inverse Agonism - As described above, nimacimab is a noncompetitive inhibitor which we believe confers specific advantages.

Additionally, nimacimab can inhibit CB1 without an agonist present in which case it can drive the opposite signaling of CB1 agonists such as promoting increased cAMP and reduced b-arrestin recruitment.

Additionally, nimacimab can inhibit CB1 without an agonist present in which case it can drive the opposite signaling of CB1 agonists such as promoting increased cAMP and reducing b-arrestin recruitment.

Thus, nimacimab inhibits CB1 as both a noncompetitive antagonist and an inverse agonist.

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Our Phase 2a study includes an exploratory arm evaluating the combination of Wegovy (semaglutide) with Nimacimab to assess this potential.

Preclinical Data

The CB1 pathway is clinically validated and has many supporting studies that highlight peripheral mechanisms to promote productive metabolic changes, including weight loss.

However, sufficiency of nimacimab-driven weight loss and related metabolic gains remained a critical hurdle to be addressed.

Outside of clinical studies, we endeavored to understand if nimacimab could drive weight loss using a diet-induced obesity ("DIO") mouse model.

Summary of Preclinical Data

The CB1 pathway is clinically validated to drive weight loss and has many supporting studies that highlight peripheral mechanisms to promote productive metabolic changes, including weight loss.

We endeavored to understand if nimacimab could drive weight loss using a diet-induced obesity ("DIO") mouse model.

Since nimacimab does not cross-react with mouse CB1, a transgenic mouse was generated which targeted the murine CB1 ("mCB1") loci for insertion of human CB1 ("hCB1").

This targeted disruption of mCB1 for hCB1 knockin mice was confirmed genetically as well as functionally, as measured by productive CB1 signaling in a THC-induced hyperthermia model as well as the ability to generate obese mice with a high fat diet ("HFD").

We found that the use of nimacimab in this mouse DIO model demonstrated the following:

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• significant fat mass loss with lean mass preservation;

• dose-dependent improvement in glucose tolerance.

The above figure highlights body weight and composition analyses performed with two-way analysis of variance ("ANOVA") repeated measurements.

A Tukey multiple comparison test was then performed for all pairwise comparisons.

Body weight reporting occurred at day 35 of treatment and body composition was measured with an echoMRI on day 33.

Beyond weight loss and productive body composition, the above data demonstrates positive changes in glycemic control with a dose-dependent improvement in glucose tolerance in obese mice.

Day 27 mice fasted for four hours before receiving an intraperitoneal injection of 10 grams of glucose with measurement of blood glucose over 120 minutes as part of the glucose tolerance test ("GTT").

GTT analyses included (1) a two-way ANOVA repeated measurements (a Tukey multiple comparison test) and (2) a baseline subtracted area under the curve ("AUC") analysis performed with a one-way ANOVA with a Tukey multiple comparison test.

In addition to clinical data sets from monlunabant and rimonabant, this DIO data supports the hypothesis that peripheral CB1 inhibition is sufficient for weight loss while central CB1 inhibition is not required for metabolic improvements such as weight loss.

Instead, this data suggest that central CB1 inhibition may only minimally contribute to efficacy, yet is likely to be a driver of neuropsychiatric adverse events.

• dose-dependent glycemic improvements

Furthermore, an additional preclinical mouse DIO study provided further evidence for the potential combination of nimacimab with incretins and demonstrated the potential durability of response with nimacimab as a monotherapy or maintenance therapy post-incretin treatment.

This preclinical mouse DIO study demonstrated that at day 25 the combination of nimacimab and a suboptimal tirzepatide dose (3nmol/kg daily) yielded 44% vehicle-adjusted weight loss (29.6% weight loss).

The combination outperformed either agent alone with nimacimab demonstrating 21.5% vehicle-adjusted weight loss (7.1% weight loss) and the suboptimal tirzepatide dose demonstrating 29.7% vehicle-adjusted weight loss (15.4% weight loss).

The combination efficacy also exceeded an optimal dose of tirzepatide (10 nmol/kg), which resulted in 38.9% vehicle-adjusted weight loss (24.6% weight loss).

The preclinical mouse DIO study also demonstrated that, when used as a monotherapy, nimacimab-driven weight loss persisted for about 20 days after treatment cessation, while mice treated with tirzepatide alone regained most of their lost weight within a week post-treatment.

Lastly, the preclinical mouse DIO study demonstrated that when nimacimab alone was used after an initial tirzepatide or combination treatment in the preclinical mouse DIO mouse model, it reduced rebound weight gain in these groups of mice.

In addition to clinical data sets from monlunabant and rimonabant, we believe these DIO data support the hypothesis that peripheral CB1 inhibition is sufficient for weight loss while central CB1 inhibition is not required for metabolic improvements such as weight loss.

Nonclinical Data

Two Investigational New Drug Applications ("IND")-enabling nonclinical studies with nimacimab were completed in non-human primates, which demonstrated a strong safety profile with a no adverse effect level ("NOAEL") of 75 mg/kg.

In addition, nimacimab was shown in two independent non-human primate biodistribution studies to have almost no exposure in the brain (~0.02%), with multi-dose studies demonstrating no accumulation.

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Taken together, we believe these nonclinical studies demonstrate that nimacimab is safe, with an NOAEL of 75 mg/kg, and that very little, if any, nimacimab enters the CNS.

Clinical Data

Clinical Development History of Nimacimab

Summary of Completed Phase 1 Studies

In June 2017, Bird Rock initiated a Phase 1b study.

The purpose of the study was to evaluate the safety and tolerability of multiple doses of nimacimab after four weeks of dosing in subjects with non-alcoholic fatty liver disease ("NAFLD"), now known as metabolic-associated fatty liver disease ("MAFLD").

Secondary objectives included determination of pharmacokinetics of nimacimab for multiple doses and to determine levels of anti-drug antibodies ("ADA") after dosing with nimacimab.

The study was carried out in subjects who had baseline NAFLD.

The study was carried out in subjects who had baseline MASLD.

This was done to enable the preliminary assessment of biomarkers of liver disease with short term therapy.

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In Part A of this study, 24 healthy volunteers were randomized to receive a single dose of either placebo or single ascending doses of nimacimab (0.6, 1.2 or 2.5 mg/kg).

In Part B of this study , 82 pat ients with pre-diabetes or diabetes and NAFLD were randomized to receive either placebo or multiple escalating doses of nimacimab (0.6, 1.2 or 2.5 mg/kg) once a week for four weeks.

In Part B of this study , 82 pat ients with pre-diabetes or diabetes and MASLD were randomized to receive either placebo or multiple escalating doses of nimacimab (0.6, 1.2 or 2.5 mg/kg) once a week for four weeks.

There were no deaths, serious adverse events ("SAEs") or treatment-emergent adverse events ("TEAEs") that lead to discontinuation.

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Only two subjects had consistently elevated titers over multiple time points of ADA.

This data suggest that nimacimab has overall low immunogenicity.

This data suggest that nimacimab has an overall low immunogenicity profile.

The placebo group in the Phase 1 study had an increase in weight while the treatment groups showed stable weight resulting in a numerical difference that represents an early trend for potential efficacy.

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No significant treatment effect was observed on liver fat percentag e, de-novo lipogenesis, i nflammatory biomarkers and OGTT test.

We believe the preliminary trends seen in the Phase 1 study, over a short duration of treatment, demonstrated the potential for nimacimab to have similar or greater effects on modulation of weight and treating conditions known to be associated with obesity.

Full study data was presented at the European Association for the Study of Diabetes ("EASD") Annual Meeting in September 2025.

Summary of Phase 2a Study

In October 2025, we announced the results from our CBeyond Phase 2a proof-of-concept clinical trial of nimacimab administered as a subcutaneous injectable for the treatment of obesity and overweight in the United States.

CBeyond is a randomized, placebo- and active-controlled, double-blind Phase 2a trial that enrolled 136 adults with obesity or overweight, including individuals with a BMI ≥27 kg/m² with at least one comorbidity.

Patients were randomized across four arms, 2:2:1:1 to arms with weekly nimacimab 200 mg subcutaneously, placebo, nimacimab 200 mg plus semaglutide (Wegovy®), or placebo plus semaglutide, and were dosed weekly for 26 weeks.

Patients not participating in a 26-week extension were monitored for 13 weeks post-treatment.

We reported the following 26 week data from the CBeyond Phase 2a study :

• The nimacimab monotherapy arm did not achieve the primary endpoint of weight loss compared to placebo (-1.52% vs.

-0.26 for placebo, mITT).

Preliminary pharmacokinetic analysis suggested an association between exposure and response, indicating that the 200 mg, subcutaneous weekly dose was suboptimal as a monotherapy.

• At the tested dose and exposure levels, nimacimab 200 mg demonstrated a favorable safety profile with placebo-like tolerability.

In combination with semaglutide, there was no increase in gastrointestinal (GI) adverse events.

Importantly, there were no increases in neuropsychiatric adverse events reported resulting from treatment with nimacimab.

• In the combination arm, nimacimab 200 mg, subcutaneous weekly dose plus semaglutide demonstrated a clinically meaningful magnitude of weight loss compared to semaglutide alone (-13.2% vs -10.25%, p=0.0372, mITT), with no plateau being observed through Week 26.

In the combination arm, 100% of patients achieved greater than 5% weight loss (vs.

85% with semaglutide alone) and 67% achieved greater than 10% weight loss (vs.

50% with semaglutide alone) based on the per protocol analysis.

This finding supports potential further studies to evaluate combinations of nimacimab and incretin-based therapies, like semaglutide or tirzepatide.

Other findings in the combination arm included:

◦ Nimacimab plus semaglutide showed a change of -11.26cm (1.16cm) in waist circumference versus -8.09cm (1.2cm) for semaglutide alone, resulting in a difference of -3.17cm (1.59cm) (p=0.0492, using least-squares mean (LSM)).

◦ An improvement in lean mass to fat mass ratio was observed at week 26 when comparing the nimacimab plus semaglutide combination arm to the placebo arm (0.26 vs.

0.02, p <0.0001), and the combination arm compared to semaglutide alone (0.26 vs.

0.13, p = 0.0126).

◦ A decrease in rebound weight gain in an analysis of participants 12 weeks post-treatment when nimacimab 200 mg (subcutaneous, weekly) was combined with semaglutide when compared to semaglutide alone (17.8% versus 37.3% weight rebound).

Moreover, at 12 weeks post-treatment, the nimacimab plus semaglutide group maintained significant weight loss compared to the placebo group (p=0.006), while the semaglutide alone group lost significance over the placebo group (p=0.12) and followed a trajectory of rebound weight gain consistent with previously reported data (Wilding et al., 2022, STEP-1 Trial Extension), which demonstrated that patients will gain a majority of weight back within 1-year of stopping treatment with semaglutide.

Topline data from our CBeyond Phase 2a study was presented at ObesityWeek medical conference in November 2025.

Summary of Phase 2a Extension Study

Patients who completed 26 weeks of treatment in the Phase 2a study were eligible to enroll in a 26-week extension for a potential full treatment duration of 52 weeks with a 13-week follow-up period.

A total of 43 patients were enrolled, with 19 and 24 patients in the combination and monotherapy cohorts, respectively.

In the combination arms, continued with blinded treatment with nimacimab or placebo and continued receiving semaglutide (Wegovy®).

Patients in the monotherapy arm received nimacimab 300 mg during the extension.

In February 2026, the Company reported the following interim results from the combination cohort of its Phase 2a extension study:

• 19 participants in the combination cohorts completed week 26 were eligible for, and enrolled in the extension study, which continued in a blinded manner for 26 weeks, maintaining their original treatment assignment (10 nimacimab plus semaglutide;

9 placebo plus semaglutide).

An additional 22 participants completed week 26 and were either ineligible for the extension or chose not to join the extension study and continued on post-treatment follow-up (11 nimacimab plus semaglutide;

11 placebo plus semaglutide).

• Of the 10 participants in the nimacimab plus semaglutide arm who joined the extension study, the mean weight loss at 26 weeks was 14.4%.

7 participants completed the additional 26 weeks of treatment and lost an additional 7.9% of weight, resulting in a mean weight loss of 22.3% after 52 weeks of treatment.

According to initial results in this limited cohort, the combination therapy remained safe and well tolerated.

No SAEs or AESIs were reported during the extension period.

• Of the 9 participants in the placebo plus semaglutide arm that joined the extension study, mean weight loss at 26 weeks was -13.9%.

7 participants completed treatment of the additional 26 weeks and lost an additional -5.8% of weight during the extension period, resulting in a mean weight loss of -19.7% after 52 weeks of treatment.

Full topline reporting of the CBeyond Phase 2a extension data including nimacimab monotherapy data and 13-week off-therapy follow-up is expected to take place in the third quarter of 2026.

Clinical Development Plan

In August 2024, we initiated a 26 week Phase 2a proof-of-concept trial with a 13 week follow up, CBeyond TM for nimacimab in obesity.

The CBeyond TM clinical trial recruited approximately 136 evaluable patients in 16 clinical trial sites to assess differences in weight loss, body composition, and other attributes.

This CBeyond TM clinical trial's primary endpoint is to evaluate weight loss using nimacimab compared to placebo.

Secondary endpoints include evaluations of safety and tolerability, neuropsychiatric and cognitive evaluation, change in body composition by Dual-Energy X-ray Absorptiometry ("DEXA"), and changes in key metabolic biomarkers such as triglycerides, and insulin and leptin sensitivity.

Patients will also be recruited to an exploratory combination arm with a GLP-1 agonist.

To obtain 52 weeks of treatment data, the Company is planning a trial extension that increases the originally planned 26 weeks of treatment to provide a longer-term assessment of safety, tolerability and efficacy.

The protocol extension will provide for continued assessment for all four treatment arms including both the nimacimab monotherapy (primary endpoint) and the nimacimab/GLP-1 combination cohort (exploratory endpoint).

The biopharmaceutical industry is intensely competitive and is characterized by rapid technological progress.

In March 2026, we initiated an expansion study (Part C) of the CBeyond Phase 2a trial to assess preliminary safety and pharmacokinetic (PK) profile of nimacimab administered intravenously (IV).

The expansion study will co mprise two cohorts of nimacimab monotherapy (400 mg IV and 600 mg IV) compared to placebo administered weekly over 15 weeks (16 doses), with a 12 week follow up period, to generate preliminary monotherapy safety, PK, and exploratory efficacy data.

Within each dose cohort, 8 participants will be randomized in a 3:1 ratio to nimacimab (n=6) or placebo (n=2).

We expect to report topline data from the expansion study in the fourth quarter of 2026.

We have received comments from the agency regarding our Type C meeting request in which they responded to our proposed Phase 2b clinical trial design, we intend to use data from the CBeyond trial, including the CBeyond expansion study (Part C), to inform the design of a potential Phase 2b study and potential registration path for nimacimab as a combination therapy with GLP-1s.

Key design elements under evaluation include patient selection, dose selection, treatment duration, and endpoints.

Final trial design and timing remain subject to ongoing data analysis, regulatory feedback and capital considerations.

The biopharmaceutical and pharmaceutical industries are intensely competitive and characterized by rapid technological progress.

In general, competition among pharmaceutical products is based in part on product efficacy, safety, reliability, availability, price and patent position.

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We also depend upon our ability to attract and retain qualified personnel, obtain patent protection or otherwise develop proprietary products or processes and secure sufficient capital resources for the often substantial period between technological conception and commercial sale.

While we believe that our knowledge, experience and scientific resources provide us with competitive advantages, we face competition from major pharmaceutical and biotechnology companies, academic institutions, governmental agencies and public and private research institutions, among others.

If nimacimab is approved for the indications for which we expect to conduct clinical studies, it will compete with the foregoing therapies and currently marketed drugs, as well as any drugs potentially in development.

It is also possible that we will face competition from other pharmaceutical approaches as well as other types of therapies.

The key competitive factors affecting the success of our program, if approved, is likely to be its efficacy, safety, differentiation, convenience, price, level of generic competition, and availability of reimbursement.

Despite significant biopharmaceutical industry investment, no therapy targeting CB1 has been approved for the treatment of obesity in the US.

Large and established pharmaceutical companies are developing GLP-1 agonists or combinations with other incretin-mimetics, which compete in the same market as our product candidates.

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Based on the recent FDA guidance, companies who wish to receive marketing approval for lean mass preservation must obtain acceptance from the FDA as to the appropriate primary endpoints, while the FDA guidance for drugs approved for weight loss in the overweight and obese population remains unchanged and clearly defined.

The development and commercialization of therapies for the treatment of obesity and overweight is highly competitive.

Our product candidate, nimacimab, if approved, will face significant competition, including from well-established, currently marketed therapies that have been developed by large, well-known pharmaceutical companies, and our failure to demonstrate a meaningful improvement to the existing standard of care may prevent us from achieving significant market penetration.

In particular, there is intense competition in the obesity and overweight field, especially with the advent of GLP-1 RAs, such as Wegovy, marketed by Novo Nordisk, and Zepbound, marketed by Eli Lilly.

In addition to injectable therapies for overweight and obesity, Wegovy became the first FDA approved oral GLP-1 receptor agonist in December 2025 and other oral therapies are in development for treating overweight and obesity, including those being development by Eli Lilly, Structure Therapeutics, and Viking Therapeutics.

There are numerous other companies that have commercialized or are developing treatments for obesity and overweight that we will compete with.

Competitors to nimacimab that are targeting peripheral inhibition of CB1 for the treatment of obesity and metabolic conditions include Novo Nordisk and their development effort of monlunabant.

We face competition from these companies and other major pharmaceutical and biotechnology companies, including specialty pharmaceutical companies, academic institutions, governmental agencies and public and private research institutions, among others.

Refer to " Risks Related to Commercialization — We face significant competition from entities that have made substantial investments into developing novel treatment for patients with obesity and overweight, including large pharmaceutical companies with approved therapies in our current indications, and biopharmaceutical, specialty pharmaceutical and biotechnology companies developing novel treatments and technology platforms.

If the companies develop competing technologies or product candidates more rapidly than we do or their technologies are more effective, our ability to develop and successfully commercialize products may be adversely affected" in our Risk Factors section for additional information.

Manufacturing

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We believe that our collaborative approach with leading CMOs and other partners involved in our chemistry, manufacturing and controls ("CMC") operations, positions us to reliably meet future clinical and commercial demand for nimacimab and further optimize its potential for the treatment of obesity, overweight, and related metabolic disorders.

Halozyme License Agreement

In December 2025, the Company entered into a Non-exclusive Global Collaboration and License Agreement (the “Halozyme License Agreement”) with Halozyme, Inc.

(“Halozyme”).

Under the terms of the Halozyme License Agreement, Halozyme granted the Company a non-exclusive license to Halozyme’s ENHANZE® drug delivery technology for the development of a subcutaneous co-formulation with nimacimab (such combination, the “Product”).

Halozyme will also be the Company’s exclusive supplier of clinical and commercial supplies of the active pharmaceutical ingredient ("API") for Halozyme’s rHuPH20 bulk drug product.

Among other considerations, the Company will make milestone payments to Halozyme tied to achievement of certain development and commercialization milestone events with respect to the Product, as well as milestone payments based on achievement of certain net sales levels of the Product.

The Company will also make mid-single digit royalty payments based on worldwide net sales of the Product.

To date, none of such milestones has been achieved.

The Halozyme License Agreement became effective in December 2025 and, unless earlier terminated, will continue until the expiration of the royalty term for the applicable product in each country, which begins upon the first commercial sale of the product in such country and continues until the last valid patient claim covering the product in that country or the length of time specified in the Halozyme License Agreement.

The Halozyme License Agreement also includes customary termination rights, representations and warranties, covenants and indemnification obligations for a transaction of this nature.

Intellectual Property

The success of most of our product candidates will depend in large part on our ability to, obtain and maintain patent and other legal protection for the proprietary technology, inventions and improvements we consider important to our business, prosecute our patent applications and defend any issued patents we obtain, preserve the confidentiality of our trade secrets, and operate without infringing the patents and proprietary rights of third parties.We strive to protect the proprietary technologies that we believe are important to our business, including seeking and maintaining patent protection intended to cover the compositions of matter of our product candidates, their methods of use, related technologies, and other inventions that are important to our business.

The success of our product candidates will depend in large part on our ability to obtain and maintain patent and other legal protection for the proprietary technology, inventions and improvements we consider important to our business, prosecute our patent applications and defend any issued patents we obtain, preserve the confidentiality of our trade secrets, and operate without infringing the patents and proprietary rights of third parties.

We strive to protect the proprietary technologies that we believe are important to our business, including seeking and maintaining patent protection intended to cover the compositions of matter of our product candidates, their methods of use, related technologies, and other inventions that are important to our business.

We employ a comprehensive approach to intellectual property protection and obtaining patent protection is not the only method that we utilize to protect our proprietary rights and technologies.

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patents, 30 granted foreign patents, including granted patents in Europe, Japan, Korea and China, as well as other commercially relevant jurisdictions, and 10 pending U.S.

and foreign patent applications directed to the compositions of matter for the nimacimab antibody and molecular variants, and to methods of treatment and uses of nimacimab and its variants for treating a number of diseases responsive to the modulation of the CB1 receptor, including obesity and related metabolic conditions.

an d foreign patent applications directed to the compositions of matter for the nimacimab antibody and molecular variants, and to methods of treatment and uses of nimacimab and its variants for treating a number of diseases responsive to the modulation of the CB1 receptor, including obesity and related metabolic conditions.

The patents, and, if issued, the patent(s) resulting from the pending patent applications will expire between 2035 and 2036, excluding any potential available patent term adjustment or patent term extension.

The use of nimacimab in therapeutic doses and methods for treating obesity and weight related comorbidities is further covered in an international (PCT) patent application owned by us and from which we expect to file U.S.

The use of nimacimab in therapeutic doses and methods for treating obesity and weight related comorbidities is further covered in two international (PCT) patent applications owned by us and from which we expect to file U.S.

and other national-phase patent applications in commercially relevant jurisdictions.

If issued, the patent(s) resulting from the pending application have an expiration date of no earlier than 2045, excluding any potential patent term adjustment or patent term extension.

If issued, the patent(s) resulting from the pending applications have an expiration date of no earlier than 2045, excluding any potential patent term adjustment or patent term extension.

The use of nimacimab in a method of predicting whether a patient is at risk for developing Fast Progressing Renal Disease ("FPRD") and treating patients to avoid such risks is further covered in pending applications in the United States, Europe, Japan and Korea, as well as other commercially relevant jurisdictions.

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In addition, our injectable product candidates are being developed together with an injector device, which will render them combination products with a device component.

We also are focusing our development efforts on at least one product candidate as a therapy intended to be used in combination with GLP-1 receptor agonists (and potentially other anti-obesity therapies).

Even where such therapies are not physically combined or co-packaged with our product candidates, seeking approval for use in combination may require additional clinical and nonclinical evidence and could increase development time, cost, and regulatory risk.

Specifically, under regulations issued by the FDA, a combination product may include:

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Following approval of a combination product, each component of a combination product retains its regulatory status (as a biologic, drug or device, for example) and is subject to the requirements established by the FDA for that type of component.

A combination product candidate with a biologic primary mode of action, as we expect our combination products to be regulated, generally would be reviewed and approved pursuant to a BLA.

Combination products require coordination within the FDA for review of each of their components (e.g., drug, device and/or biologic components) that would ordinarily require review by different FDA centers if authorized as standalone products, and this coordination may result in additional delays due to regulatory timing constraints and uncertainties in the product development and approval process.

A combination product candidate with a biologic primary mode of action generally would be reviewed and approved pursuant to a BLA.

However, the applicable approval pathway for a product candidate may be a BLA or an NDA, depending on FDA’s determination of, among other things, the product’s primary mode of action and constituent parts, and we cannot predict with certainty how FDA will classify any of our product candidates.

In reviewing the BLA for such a product, however, FDA reviewers in the biologic center could consult with their counterparts in the drug or device centers to ensure that the drug and device component of the combination product candidate, as applicable, met all requirements applicable to its category.

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Patent term restoration, however, cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.

The patent term restoration period is generally one half the time between the effective date of an IND and the submission date of a BLA plus the time between the submission date of a BLA and the approval of that application, except that the review period is reduced by any time during which the applicant failed to exercise due diligence.

The patent term restoration period is generally one half the time between the effective date of an IND and the submission date of a BLA plus the time between the submission date of a

BLA and the approval of that application, except that the review period is reduced by any time during which the applicant failed to exercise due diligence.

Only one patent applicable to an approved drug is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent.

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There is also significant uncertainty related to the insurance coverage and reimbursement of newly approved products and coverage may be more limited than the purposes for which the medicine is approved by the FDA or comparable foreign regulatory authorities.

In the United States, CMS, an agency within the DHHS, determines whether and to what extent a new medicine will be covered and reimbursed under Medicare and private payors tend to follow CMS to a substantial degree.

In the United States, the Centers for Medicare and Medicaid Services ("CMS"), an agency within the Department of Health and Human Services ("HHS"), determines whether and to what extent a new medicine will be covered and reimbursed under Medicare and private payors tend to follow CMS to a substantial degree.

Factors payors consider in determining reimbursement are based on whether the product is:

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Such scrutiny has resulted in several recent Congressional inquiries, presidential executive orders and proposed and enacted federal and state legislation and regulations designed to, among other things, reduce the cost of prescription drugs under Medicare, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products.

Most recently, on August 16, 2022, President Biden signed the Inflation Reduction Act of 2022, or IRA, into law.

Most recently, on August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 ("IRA"), into law.

Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap;

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We anticipate that we will need to hire additional employees or independent contractors for our continued development efforts.

We also intend to utilize independent contractors and outsourced services, such as CROs and third party manufacturers, where possible and appropriate.

We also intend to utilize independent contractors and outsourced services, such as contract research organizations ("CROs") and third party manufacturers, where possible and appropriate.

Corporate Information

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business