How does Acrivon fit in the larger landscape of life sciences and what is the main vision that drives the company presently?
PBJ: We are a clinical stage oncology company with a pioneering precision medicine platform, called Acrivon Predictive Precision Proteomics (AP3) that we apply for development of our drug pipeline. The AP3 platform enables us to generate our proprietary OncoSignature® companion diagnostic tests which are designed to accurately match our therapies with the patients who are predicted to benefit from each of them without relying on underlying genetic information.
Our method is designed to overcome the limitations of traditional genetics-based approaches, which have proven insufficient for the vast majority of cancer patients where there is no simple correlation between genetic alterations and the tumor progression.
We believe our proteomics-based AP3 approach is a broadly applicable method to identify patient responders to therapeutics where genetics-based approaches have fallen short, and on the basis of that we have established a pipeline of targeted oncology agents, including a lead asset which has shown durable monotherapy clinical activity in solid tumors, but genetics-based response prediction has been unsuccessful.
Kristina and I met about seven years ago. She had also been thinking deeply about the challenge of attrition in Phase 2 trials - the development phase where most drugs fail due to insufficient overall response rate. In 2018 we joined forces and founded Acrivon Therapeutics, headquartered in the US where all clinical development initially takes place and with a subsidiary in Lund, Sweden led by Kristina which is where our biomarker identification and drug discovery take place.
KM: Peter and I both have an extensive background in what is called protein signal transduction, the regulatory pathways in normal cells that govern cellular processes and that tend to go awry in cancer. Our AP3 approach is a functional, pathway-based approach aiming to link the mechanism of action of drug candidates with the underlying signaling pathways that the tumor depends on for its continued growth and expansion. At the core of our scientific approach is the measurement of protein activity states as opposed to assessing genetic alterations. This is a strong differentiating factor for Acrivon. We are convinced that measuring protein disease-driving pathways directly is a more broadly applicable, predictive method, and this led to the creation of our AP3 platform for generation of our drug-tailored OncoSignature companion diagnostic tests.
Why is patient selection so crucial for development, and how does your platform help more specifically?
PBJ: The holy grail, not just in oncology but in all disease areas, comes up in Phase 2 trials where you have to prove that your drug is active and benefits a sufficient proportion of patients to justify bringing it to market. Our platform is designed and developed to address this huge unmet need and to go beyond what genetics can do in this field.
Our drug-tailored OncoSignature tests are composed of three biomarkers each of which are required but not sufficient for prediction of sensitivity. When all three are elevated at a minimum level we predict that the tumor depends on the drug target, and thereby its sensitivity to the drug.
Your lead candidate is ACR-368; how far ahead are you with development, and what else is currently in your pipeline?
PBJ: Correct, our pipeline includes the advanced Phase 2 lead program, ACR-368 (prexasertib), a clinically active CHK1/2 inhibitor, as well as two preclinical programs targeting WEE1 and PKMYT1, all critical nodes involved in DNA Damage Response (DDR) and cell cycle regulation
Since we were able to leverage all the ACR-368 data from past trials (over 400 patients treated at recommended Phase 2 dosage, or RP2D), we received FDA clearance for using the RP2D in our Phase 2 trials. ACR-368 has shown clinical monotherapy activity in patients with platinum-resistant ovarian cancer, and using our OncoSignature test for screening we have identified endometrial and bladder cancer as two additional tumor types predicted sensitive to ACR-368. We have received clearance to pursue all 3 cancer indications in single arm studies where we intend to dose OncoSignature-positive patients with ACR-368 based on predicted sensitivity to ACR-368. The drug has also shown clinical activity in squamous cell cancers and sarcomas, so it has broad activity across tumor types.
KM: We run our co-crystallography-driven preclinical programs targeting WEE1 and PKMYT1 out of SwedenMYT1. We believe that genetics-based patient selection methods are challenging for these targets as well, and moreover, they are potentially involved in resistance to CHK1/CHK2 inhibition. We intend to leverage our OncoSignature tests to predict monotherapy activity in patients and also make rational drug combinations to overcome potential drug resistance.
Congratulations on your recent IPO. What motivated this step?
PBJ: We believe the company has a solid foundation and meaningful fundamentals , including a clinical stage asset in a registrational intent trial, a rapidly emerging preclinical pipeline behind it, and a differentiated patient selection platform. The IPO provides for additional visibility on our programs and financially further supports their advancement. It has been a tough market for funding over the last 18 months so we are proud of what we have achieved; we had an oversubscribed Series B round in November 2021 and followed up with the IPO this year.
What is your key pieces of advice to budding biotech entrepreneurs or seasoned industry-veterans?
KM: Not always just following the trends, and staying faithful to data give a real chance of becoming successful and we plan to follow this path in the coming years. Acrivon was strategically built to be nimble and capital-efficient, and the goal is to use these cultural pillars to our advantage and remain focused on the mission.
PBJ: When innovating, it is critical to remain 100% data- and science-driven and have enormous resilience, perseverance and stamina. When it comes to science, it is impossible to cut corners if you want to have a meaningful impact on patients’ lives, and we are determined to honor this principle to the very end.
