Inside preclinical CVMD innovation: A Q&A with Dr. Laura Crawford on integration strategies for advancing cardio‑kidney‑metabolic therapies

In this edition of our R&D Insight Series, we spoke with Dr. Laura Crawford, a senior scientific leader in Labcorp’s Cardiovascular & Metabolic Disease (CVMD) group, to discuss emerging trends in CVMD drug development, the complexities of the cardio‑kidney‑metabolic (CKM) continuum, and how integrated nonclinical strategies are helping sponsors move faster with greater confidence.

Q1: Cardiovascular and metabolic diseases rarely occur in isolation. How does this complexity shape preclinical/nonclinical development?

Dr. Crawford:
That’s exactly right. The most significant challenge today is that cardiovascular, kidney, and metabolic conditions don’t exist as siloed diseases. They intersect across what we refer to as the CKM continuum, where factors such as obesity, diabetes, dyslipidemia, hypertension, and renal dysfunction amplify overall risk and can alter therapeutic response.

From a nonclinical safety perspective, this means we can’t treat cardiovascular safety, metabolic pharmacology, or GI tolerability in isolation. Because these systems are interdependent, nonclinical study designs must assume that multiple systems may be affected simultaneously. Sponsors increasingly need integrated study designs that intentionally combine endpoints across systems, including:

• Cardiovascular and electrophysiology endpoints
• Metabolic function and glucose dynamics
• GI tolerability and gastric emptying (especially for incretin‑based mechanisms)
• Biomarkers spanning inflammation, appetite regulation, and metabolic stress

In practice, this requires prospectively incorporating these endpoints into the same study, with appropriate group sizes, sampling timepoints, and endpoint selection to enable cross-system assessment. This includes aligning collection timepoints to capture cardiovascular endpoints (e.g., ECG, blood pressure) alongside metabolic readouts, while also monitoring GI effects such as food intake or gastric emptying.

It also requires deliberate model selection and consideration of baseline physiology, as healthy versus disease-relevant models can meaningfully impact interpretation of safety and pharmacology signals. Our role is to help sponsors design nonclinical safety packages that reflect this complexity while remaining interpretable, efficient, and fit-for-purpose for regulatory decision-making.

Q2: Where do the biggest translational risks tend to arise for CVMD therapeutics?

Dr. Crawford:
There are three major risk areas:

1. Model relevance
Cardiometabolic diseases develop over decades in humans, while preclinical efficacy and safety studies necessarily compress those processes into shorter-term models. The key challenge is recognizing that no single model fully reflects the clinical setting, so the data always needs to be interpreted within the context of the model’s limitations. For example, efficacy for incretin-based therapies is often demonstrated in diet-induced obesity or diabetic models that reflect key metabolic features of disease. However, those same models can introduce baseline variability that complicates interpretation of endpoints, particularly for safety readouts such as cardiovascular parameters or clinical pathology.

2. Interpretation of nonclinical safety signals
CVMD therapies often require cardiovascular, metabolic, and GI signal monitoring simultaneously. It can be challenging to collect these endpoints in the same study and interpret them in context, especially when a pharmacologic effect in one system influences readouts in another. For example, GLP‑1 and dual incretin compounds may influence cardiac conduction, gastric emptying, appetite regulation, and inflammatory pathways, all of which must be evaluated together for nonclinical safety.

3. Comorbidities
As we’ve discussed, a therapy that appears clean in a simple model may behave differently in the presence of comorbidities such as obesity, hepatic stress, or renal impairment. This is particularly important in CVMD, where these conditions are often intrinsic to the target patient population rather than secondary considerations. As a result, nonclinical safety evaluation requires a cross-disciplinary approach to data interpretation to appropriately de-risk therapies and avoid missing clinically relevant signals.

Labcorp’s integrated CVMD platform is designed specifically to support cross-functional assessment and mitigate these translational gaps.

Q3: GLP‑1 and incretin‑based mechanisms are evolving rapidly. What specialized tools does Labcorp offer in this space?

Dr. Crawford:
GLP-1 receptor agonists and broader incretin-based therapies are undergoing rapid advancement, with increasingly complex mechanisms that impact not only metabolic pathways, but also GI and cardiovascular physiology. As a result, nonclinical evaluation requires tools that characterize both pharmacologic activity and safety across these interconnected systems. We’ve built a suite of focused capabilities to address these areas, including:

• Gastric emptying measurements
• Gastric damage assessment
• Gastric secretion (rat)
• Combined GI transit + gastric emptying studies (rat and mouse)
• Integrated cardiovascular endpoints, including heart rate, blood pressure, ECG intervals (PR, QRS, QT/QTc), and arrhythmia monitoring using GLP‑compliant rodent and large‑animal telemetry
• Appetite‑regulation and metabolic biomarkers: glucose, inflammatory, insulin, thyroid
• DEXA body‑composition analysis
• Adiposity assessment
• Proactive animal‑welfare and risk‑mitigation strategies for expected weight‑loss effects 

These endpoints help provide a complete picture of therapeutic tolerance and mechanism. Bringing them together helps us better understand how these therapies are likely to perform in the clinic.

Q4: How do biomarkers strengthen the translational bridge between preclinical and clinical development?

Dr. Crawford:
Biomarkers are central to CVMD development. They help anchor preclinical efficacy and/or nonclinical safety signals to clinical outcomes. In a therapeutic area where translational risk is high, biomarkers provide a way to anchor pharmacologic and safety signals across stages of development. Our teams routinely combine:

• Mechanistic biomarkers tied to drug targets
• Pharmacodynamic biomarkers (e.g., glucose/insulin dynamics, appetite‑regulation peptides)
• Cardiac safety biomarkers
• Inflammatory markers relevant to CKM burden

The value is not just in measuring these biomarkers, but in selecting and incorporating them early so that nonclinical readouts can be directly compared to clinical endpoints. Because Labcorp also supports diagnostic CVMD biomarker testing in clinical populations, we can ensure early‑stage biomarker strategies directly map to anticipated clinical measures. This is a major translational advantage.

Because cardiometabolic diseases share overlapping biology across cardiovascular, renal, metabolic, and endocrine systems, these biomarker strategies are intentionally designed for broad applicability. They scale seamlessly from nonclinical studies into central lab–supported cardiometabolic clinical development. This approach enables shared biomarkers, a consistent assay strategy, and more streamlined trial execution as programs advance.

Q5: Telemetry remains a cornerstone of cardiovascular safety. How is Labcorp advancing this capability?

Dr. Crawford:
Telemetry is a central component of cardiovascular safety, particularly as therapies become more complex and effects on cardiac function may be subtle or indirect. Labcorp has invested heavily in cardiovascular safety infrastructure. That includes:

• GLP‑compliant telemetry across rodent and large‑animal platforms
• Jacket‑free ECG/hemodynamic collection (PhysioTel™ M‑series)
• Concentration–QTc modeling
• Rodent and nonrodent echocardiography
• Centralized ECG interpretation for consistency and expert review

These capabilities allow us to detect subtle cardiovascular signals earlier and integrate CV endpoints into toxicology packages where appropriate. This supports efficient study design and regulatory decision-making, enabling sponsors to address potential risks early and reduce downstream time and cost.

Q6: How does Labcorp use its capabilities to help sponsors make better early decisions and maintain development speed?

Dr. Crawford:
We partner with sponsors early to design fully integrated nonclinical CVMD programs. These programs align scientific strategy, regulatory expectations, and development timelines, particularly for therapeutics where cardiovascular, metabolic, and GI considerations are inherently linked. This means defining study strategies that incorporate these endpoints from the outset and bringing cross‑disciplinary teams together to design and execute studies with the end in mind.

This integrated approach allows us to generate a single, cohesive dataset that supports mechanistic understanding, safety decision‑making, and IND‑enabling discussions without the need for redesign or fragmented follow‑up studies. In practice, that integration shows up through:

• Coordinated CV, metabolic, and GI pharmacology designed as one program, not isolated studies
• Dedicated GLP telemetry with centralized ECG interpretation for consistent, decision‑ready CV data
• Cross‑disciplinary scientific teams linking safety, PK/PD, biomarkers, and pathology
• Early mechanistic insight from NAM platforms, including microfluidic vascular models
• Regulatory‑ready outputs, including SEND‑compliant datasets and digital pathology

Just as importantly, this structure creates continuity into early clinical planning, where aligned biomarker strategies and regulatory context can be carried forward without loss of momentum or translational clarity. Because our capabilities are integrated from study design through regulatory submission, and aligned with early clinical development, sponsors benefit from fewer handoffs, clearer translational narratives, and decision‑ready outputs that support both development speed and regulatory confidence.

Q7: What scientific trends are most influential in shaping the future of CVMD development?

Dr. Crawford:
Several exciting shifts in the development industry are shaping CVMD development:

1. CKM‑integrated approaches
 As we’ve discussed, sponsors are increasingly moving toward integrated design strategies that incorporate cardiovascular, kidney, liver, and metabolic endpoints together rather than evaluating each in isolation.

2. New metabolic mechanisms and incretin evolution
 We’re seeing rapid expansion of incretin-based therapies, including dual- and tri-agonists, which bring more complex GI, metabolic, and cardiovascular considerations that need to be understood in combination.

3. Mechanistic NAM tools
 There’s growing use of new approach methodologies (NAMs), including microphysiological vascular and thrombosis models, as alternative, non-animal approaches to generate earlier mechanistic insights. This is an evolving area that supports earlier decision-making and helps guide in vivo study design before more resource-intensive studies are initiated.

4. Biomarker‑driven precision
 Use of multi‑marker biomarker panels are beginning to play a larger role in aligning nonclinical and clinical data, which will ultimately support more confident as programs advance to first in human studies and beyond in the clinic.

We’re continuing to evolve our capabilities in parallel with these trends to better support integrated and translational CVMD development.

Q8: What advice would you give sponsors entering the CVMD preclinical pathway?

Dr. Crawford:
The most important recommendation is to build your translational hypothesis and workplan early and test it by efficiently executing studies so you can develop your integrated dataset, not isolated endpoints. That starts with understanding your target product profile, anticipated clinical endpoints, and the regulatory path required to get there.

The strongest programs:

• Plan backward from expected clinical endpoints
• Integrate CV + GI + metabolic safety from day one
• Use biomarkers that map directly to anticipated clinical measures
• Bring regulatory strategy into early study design
• Choose partners who can maintain continuity into early clinical phases

Equally important is having a clear view of development options, timelines, and capabilities early on and integrating those considerations into study design and execution. Taking a more end-to-end approach that aligns strategy, study execution, and regulatory planning to ensure decisions are efficient, data are interpretable, and programs stay on track as they move toward the clinic.

That’s exactly why our CVMD platform is structured the way it is: to shorten time to IND while strengthening regulatory confidence.

Closing thoughts

Cardiovascular and metabolic diseases remain among the most complex therapeutic areas, yet they are also among the most transformative. Through an integrated CVMD platform spanning cardiovascular safety, metabolic and incretin pharmacology, GI tolerability, biomarkers, NAM platforms, bioanalysis, SEND, and regulatory strategy, Labcorp serves as a single nonclinical partner, helping sponsors advance meaningful therapies with both speed and scientific confidence.

Dr. Crawford and the Labcorp scientific team continues to support sponsors across biotech and pharma by delivering integrated, decision‑grade nonclinical data and continuity into early clinical development, helping programs move forward with clarity, efficiency, and regulatory confidence.

For sponsors navigating the complexity of the CKM continuum, early integration and the right development partner can be the difference between momentum gained and risk rediscovered later. Access cardiovascular metabolic biomarker insights from Labcorp