The American Hematology Society (ASH) held its 64th Annual Meeting in December 2022. During the Meeting, a variety of stakeholders—including physicians, researchers, and industry members—gathered to discuss research, trends, and other important topics within the field of hematology.

One such presentation was given by Centessa Pharmaceuticals. The presentation shared an additional 18 months of continued treatment data from the open-label extension (OLE) of the company’s Phase 2a study of SerpinPC for patients with hemophilia. Data from the study showed a significant reduction in bleeding, as well as sustained safety, efficacy, and tolerability. Shares Dr. Antoine Yver, MD, MSc, the Chairman of Development at Centessa:

We were thrilled to have had the opportunity to share the open-label extension data for SerpinPC at the ASH Annual Meeting. ASH brings some of the greatest minds in hematology together, so the fact that we were able to debut our data at such a high-caliber event underscores the hemophilia community’s interest in potential innovative treatments with an unprecedented and new mechanism of action.

Recently, Patient Worthy spoke with Dr. Yver about Centessa’s focus on patient-centricity, the data presented at the ASH Annual Meeting, why these data demonstrate the potential of SerpinPC to offer a meaningful treatment option for hemophilia patients, and exciting pipeline developments.

About Dr. Antoine Yver, MD, MSc

Dr. Yver is a Pediatric Oncologist who earned his MD from the Université Paris-Saclay. According to his profile on the Centessa website, Dr. Yver:

brings more than 30 years of global experience in the pharmaceutical industry to Centessa and has led the approvals of 11 different drugs, including TAGRISSO, LYNPARZA, and ENHERTU. He led the development of TAGRISSO in 2 years and 7 months from first human dose to U.S. approval and its rapid deployment to all other major regions, which was the fastest ever for an anti-cancer drug. Antoine joined Centessa from Daiichi Sankyo Company, Ltd., where he served as Executive Vice President and Global Head, R&D Oncology, and Chair of the Cancer Enterprise. Antoine currently serves as an independent director on the Board of Sanofi (NASDAQ: SNY) and as an independent board member on the Board of Spotlight Therapeutics.

Prior to joining the team at Centessa, Dr. Yver also worked as Senior Vice President, Global Medicine Head, Oncology, and Global Medicines Development China Lead with AstraZeneca, as well as in various clinical development roles at companies such as Schering-Plough/Merck, Johnson & Johnson, and Aventis Pharmaceuticals.

JL: Tell me about Centessa. What brought you to the team?

Centessa is a clinical-stage pharmaceutical company focused on discovering and developing medicines that are transformational for patients. Our diversified pipeline spans discovery-stage to pivotal-stage development and is made up of programs covering a range of high unmet medical need indications, with potential to be first-in-class / best-in-class. We are driven by patient-centricity and our mission is to deliver high-impact medicines to patients in need of new treatments. By practicing an asset-centric approach to our pipeline development, we seek to pursue the best assets regardless of therapeutic area or technology.

After spending decades as a physician and in drug development top leadership with industry leaders including AstraZeneca and Daiichi Sankyo, during which I led 11 different new drugs to approval, I joined Centessa because I saw an opportunity to potentially improve patient lives with novel pharmacology. This is what I’m passionate about. Centessa’s pipeline includes assets with unprecedented and new mechanisms of action that we believe have the potential to meaningfully improve patients’ lives.

JL: I love that you take a patient-centric approach. How does Centessa work to maintain that patient-centricity in all that you do?

Our company was built from the ground-up to help patients. We are agnostic to the therapeutic area or the pharmacological platform, but intent on pursuing novel pharmacology which has a high conviction potential to address well-identified unmet patient needs. Simply put, this is the reason each one of us is here at Centessa and the mission is shared by all of us.

JL: During the ASH presentation, Centessa spoke about data from the OLE of its Phase 2a study exploring SerpinPC for hemophilia. What is SerpinPC?

SerpinPC is an investigational drug which has a novel mechanism of action and pharmacology. It is a subcutaneously administered novel inhibitor of activated protein C (APC) being developed for the treatment of hemophilia. SerpinPC is designed to prevent and reduce bleeds in persons with hemophilia.

At the recent ASH meeting, we shared an additional 18-months of continued treatment data from the OLE of our Phase 2a study of SerpinPC for hemophilia. These data show a continued favorable safety and tolerability profile for SerpinPC, as well as sustained long-term efficacy results, as measured by a reduction in the all-bleeds annualized bleed rates (ABRs) and the absence of sustained elevation of D-dimers, a measure of possible thrombosis risk.

JL: Why is SerpinPC such a meaningful and transformational treatment option for people living with hemophilia B?

Hemophilia B is a rare disease affecting an estimated 10-15,000 individuals in the US and across Europe, with a greater prevalence in other regions. These individuals have a high unmet need as limited treatment options are available – there are no alternatives to intravenous factor concentrate, and no clinically meaningful treatment option for persons with hemophilia B and a replacement factor inhibitor. Although we believe SerpinPC has the potential to treat all types of hemophilia, the initial focus of our registration efforts will be hemophilia B, with and without inhibitors. 

JL: What is the current standard-of-care for hemophilia? Why does SerpinPC present a novel and transformative option as compared to the standard-of-care?  

Of the estimated 450,000 persons with hemophilia worldwide, only 20% are believed to have access to adequate therapy. At present, factor concentrate therapies represent the standard-of-care for hemophilia and require intravenous administration, which can make treatment challenging.

SerpinPC, which is being developed for hemophilia, is designed as a long-acting non-replacement therapy intended to be administered as infrequent subcutaneous dosing that ‘rebalances’ blood coagulation without the need for factor replacement. The Phase 2a data, including data from the OLE, show a continued favorable safety and tolerability profile for SerpinPC, as well as sustained long-term efficacy results, as measured by a reduction in the all-bleeds annualized bleed rates (ABRs). We are encouraged that no thromboembolic events or treatment-related sustained elevations in D-dimer (a sensitive measure of excess thrombin generation) were observed throughout the study.

We are excited that these data support the potential for SerpinPC’s new mechanism of action to provide a clinically meaningful subcutaneous therapy to people with hemophilia B who have high unmet need and limited options.

JL: What were the most meaningful outcomes from the OLE of the Phase 2a study? Why was this data so important / why did it stick out to you? 

The OLE data from our Phase 2a study show a continued favorable safety and tolerability profile for SerpinPC, including at a higher dosing regimen, as well as sustained long-term efficacy results, as measured by a reduction in the all-bleeds annualized bleed rates (ABRs). Consistent with data from the six-month repeat dose portion of the Phase 2a study, there were no thromboembolic events and no treatment-related sustained elevations of D-dimer observed throughout the 18-month OLE period. In addition, there were no SerpinPC-related adverse events during the OLE period.

With a total exposure of over 40 patient-years across multiple dosing regimens with SerpinPC, these encouraging new long-term data add further weight to the durability of effect and sustained safety and tolerability observed to date in severe hemophilia. 

JL: How do you plan on continuing to develop SerpinPC in the future?

We are advancing the pivotal program for SerpinPC with the goal of bringing this potential therapy to individuals with hemophilia B as quickly as possible, subject to regulatory review and approval. The pivotal program for SerpinPC in hemophilia B, with and without inhibitors, includes a set of studies with multiple components. We have initiated PRESent-5, an observation feeder study to collect prospective observational data for minimum defined periods before switching to dosing subjects in the interventional studies planned for 2023. The interventional studies include PRESent-2 (moderately severe to severe hemophilia B without inhibitors, and severe hemophilia A with and without inhibitors) and PRESent-3 (hemophilia B with inhibitors).

JL: Is there anything else in your pipeline that you are particularly excited about?

Yes, of course! We believe each asset in our pipeline has potential to be a first-in-class / best-in-class therapeutic. .We are also developing LB101, our first LockBody candidate for solid tumors. LB101 is a conditionally tetravalent PD-L1xCD47 LockBody® bispecific monoclonal antibody. We have continued to share encouraging non-clinical data for LB101 which demonstrate the potential for an enhanced therapeutic index and a well-tolerated safety profile, and we look forward to building on these data and initiating a clinical trial for LB101 as quickly as possible, subject to IND clearance.

Learn more about Centessa Pharmaceuticals.