DEFA14A: Centessa Pharmaceuticals PLC Reports Progress in Pipeline Programs and Financial Results for Year Ended December 31, 2023

Centessa Pharmaceuticals PLC highlights advancements in its pipeline programs, including SerpinPC and ORX750, while reporting its financial results for the year ended December 31, 2023.

Summary

• Centessa Pharmaceuticals PLC is a clinical-stage pharmaceutical company focused on discovering and developing transformational medicines.
• The company's most advanced product candidate is SerpinPC, a subcutaneously administered novel inhibitor of activated protein C (APC) being developed as a potential treatment for hemophilia.
• Phase 2a clinical data has shown SerpinPC to have a favorable safety and tolerability profile, as well as evidence of sustained efficacy in patients with hemophilia.
• SerpinPC is now in registrational trials for the treatment of hemophilia B with and without inhibitors, PRESent-3 and PRESent-2, respectively.
• The FDA granted SerpinPC Fast Track designation for the treatment of hemophilia B.
• Centessa is also advancing its oral orexin receptor 2 (OX2R) agonist program for the treatment of narcolepsy and other sleep-wake disorders.
• The lead product candidate, ORX750, is an investigational, orally administered, selective orexin receptor 2 (OX2R) agonist for the treatment of narcolepsy.
• A Phase 1 first-in-human (FIH) clinical trial of ORX750 for the treatment of narcolepsy was initiated in April 2024.
• The company is also evaluating its proprietary LockBody technology platform, with LB101 in a Phase 1/2a FIH clinical trial for the treatment of solid tumors.
• LB206, a second LockBody development candidate, is in preclinical development.
• At 31 December 2023, the Group's total liquidity position was $256.6M, and the company expects its existing cash and cash equivalents and short-term investments will be sufficient to fund the Group's operations into 2026 without drawing on the remaining available tranches under the Oberland Capital financing agreement.

Sentiment

Score: 7

Explanation: The document presents a balanced view, highlighting both progress in clinical programs and financial results. While there are ongoing losses, the company has sufficient liquidity and anticipates key milestones in the future. The sentiment is cautiously optimistic.

Positives

• SerpinPC has shown a favorable safety and tolerability profile in Phase 2a clinical data.
• SerpinPC received Fast Track designation from the FDA for the treatment of hemophilia B.
• ORX750 mimics the function of the endogenous orexin peptide, which is often missing in individuals with narcolepsy.
• LB206 demonstrated single agent regressions of large tumors in a difficult-to-treat mouse xenograft model.
• The company has a track record of making judicious capital and resource allocation decisions.
• The company expects its existing cash and cash equivalents and short-term investments will be sufficient to fund the Group's operations into 2026.

Negatives

• The Group and the Company have incurred recurring losses and negative cash flows from operations since inception.
• The company deprioritized and paused development activities associated with CBS001, CBS004, and MGX292 in the first half of 2023.
• The company terminated MGX292 and the associated license with Cambridge Enterprise and the University of Cambridge in H2 of 2023.
• The company out-licensed the global rights to CBS004 to AnaptysBio, Inc. in November 2023.

Risks

• The company expects to continue to incur significant expenses, increasing operating losses and negative cash outflows for the foreseeable future.
• The trading price of the company's ADSs is likely to be highly volatile and could be subject to wide fluctuations in response to various factors, some of which are beyond the company's control, including limited trading volume.
• Broad market and industry factors may negatively affect the market price of the company's ADSs, regardless of the company's actual operating performance.

Future Outlook

The company anticipates key clinical milestones for its programs across 2024 and expects its existing cash and cash equivalents and short-term investments will be sufficient to fund the Group's operations into 2026 without drawing on the remaining available tranches under the Oberland Capital financing agreement.

Management Comments

• '2023 marked another year of great progress at Centessa,' said Saurabh Saha, M.D., Ph.D., Board Member and Chief Executive Officer.
• Management is committed to pursuing the best assets in a focused and capital efficient manner with the aim of delivering transformational medicines for patients.
• Management believes SerpinPC has the potential to be a first-in-class subcutaneously administered therapy with a differentiated safety profile for individuals with hemophilia B, subject to regulatory review and approval.
• Management believes ORX750 has a potential best-in-class profile for the treatment of narcolepsy and other sleep-wake disorders.
• Management remains deeply committed to keeping patients at the center of all that they do.

Industry Context

Centessa is operating in a competitive pharmaceutical industry, focusing on innovative treatments for hemophilia, narcolepsy, and solid tumors. The company's progress with SerpinPC and ORX750 positions it to potentially address unmet needs in these therapeutic areas. The company's LockBody platform represents a novel approach to bispecific antibodies, potentially offering advantages over existing therapies.

Comparison to Industry Standards

• SerpinPC aims to compete with existing hemophilia treatments by offering a subcutaneously administered therapy with a differentiated tolerability profile, potentially improving patient convenience and adherence.
• ORX750 is being developed to compete with existing narcolepsy treatments, such as stimulants and sodium oxybate, by offering a selective OX2R agonist with a potentially improved efficacy and safety profile.
• LB101 and LB206 are being developed to compete with existing PD-L1 and CD47 inhibitors for solid tumors, with the aim of selectively driving potent effector function activity into the tumor microenvironment while avoiding systemic toxicity.
• Comparable companies in the hemophilia space include Roche (Hemlibra), Novo Nordisk, and BioMarin.
• Comparable companies in the narcolepsy space include Jazz Pharmaceuticals (Xyrem/Xywav) and Avadel Pharmaceuticals (Lumryz).
• Comparable companies in the bispecific antibody space include Amgen (Blincyto) and Roche (Hemlibra).

Stakeholder Impact

• Shareholders: The company aims to drive long-term value through its pipeline programs and capital allocation decisions.
• Employees: The company is committed to attracting, incentivizing, and retaining high-caliber talent.
• Patients: The company is focused on delivering transformational medicines to patients in need.
• Suppliers and Business Partners: The company aims to build honest, respectful, and reliable relationships and arrangements.

Next Steps

• Continue registrational trials for SerpinPC in hemophilia B with and without inhibitors (PRESent-3 and PRESent-2).
• Advance ORX750 through clinical development, with the goal of sharing clinical proof of concept data in sleep-deprived healthy volunteers in 2024.
• Continue Phase 1/2a FIH clinical trial of LB101 for the treatment of solid tumors.
• Continue preclinical development of LB206.

Key Dates

Keywords

pharmaceuticals, clinical trials, SerpinPC, ORX750, LockBody, hemophilia, narcolepsy, FDA, clinical-stage, drug development