For targeted cancer therapy to work, it’s not enough to identify the right targets to hit with a drug. Just as important is selecting the patients appropriate for a given therapy. Scientists at Acrivon Therapeutics say their approach brings advantages over genetic-based patient selection. The Acrivon technology is approaching its first tests in humans with a drug acquired from a big pharmaceutical company. The IPO market, like the weather, has turned cold but Acrivon still found a way to raise nearly $100 million for its clinical trial plans.
Acrivon came close to the nine-figure IPO it wanted, but it had to slash the stock price and sell more shares in order to pull it off. This past week, the biotech offered more than 7.5 million shares for $12.50 apiece, which raised $94.4 million. When Acrivon set preliminary terms for the IPO earlier this month, it planned to offer 5.9 million shares priced in the range of $16 to $18 each.
Watertown, Massachusetts-based Acrivon was able to get closer to the $100 million mark by striking a separate and concurrent deal. Chione Limited, the largest shareholder in the company prior to the IPO, purchased 400,000 shares at the IPO price, raising another $5 million. Acrivon shares now trade on the Nasdaq under the stock symbol “ACRV.”
Matching a cancer drug to a patient is typically done according to genomics. That works when tumors have single driver mutation that causes cells to become cancerous. But Acrivon notes that more than 90% of all human cancers don’t have such mutations. Rather than looking for a genetic target, Acrivon measures proteins that are critical to tumor-driving mechanisms. The company contends this proteomics approach could be applicable to the majority of cancers that do not have genetic alterations in the drug target itself.
“Our founding vision is that proteomic biomarkers enable direct measurement of the disease-driving mechanisms and allow for accurate matching with drug action, independent of underlying genetic alterations,” Acrivon said in its updated prospectus.
The science upon which Acrivon’s technology is based stems from the research of co-founder and CEO Peter Blume-Jensen, whose pharma industry experience includes senior roles at EMD Serono and Merck & Co. In a 2001 article published in the journal Nature, Blume-Jensen and co-author Tony Hunter describe how cancer is driven by dysregulated protein signaling.
Acrivon, whose name is derived from the Greek word for “accurate,” formed in 2018. The company’s tech platform, called Acrivon Predictive Precision Proteomics, or AP3, develops tumor biopsy tests that can be used to match a drug to the patients most likely to respond to it. These tests, called OncoSignature, measure for elevated levels of proteins that a tumor depends on and that are specific to biochemical pathways addressed by a drug. Acrivon has used OncoSignature to guide the development of internally discovered drug candidates that are currently preclinical. For OncoSignature’s first test in a clinical trial, the biotech turned to molecule that stalled in the hands of Eli Lilly.
The Lilly drug, prexasertib, has a long history with multiple stops. Initially developed under a collaboration between Array Biopharma and Icos, the drug joined Lilly via the pharma giant’s $2.1 billion acquisition of Icos in 2007. The heart of that deal was blockbuster erectile dysfunction drug Cialis; prexasertib was still preclinical at the time.
Prexasertib is designed to treat cancer by interfering with a way tumors fix themselves. The rapid and uncontrollable cell growth characteristic of cancer wreaks havoc on cancer DNA. Tumors rely on DNA damage response, a repair mechanism governed by certain proteins. The Lilly drug, which Acrivon has renamed ACR-368, is designed to block CHK1 and CHK2, two proteins that temporarily stop cell replication in order to allow repair of DNA damage. Blocking these proteins prevents those repairs, leading instead to cell death.
No CHK1/2 inhibitors have been approved by the FDA yet. Lilly advanced its CHK1/2-blocking drug to multiple Phase 1 and Phase 2 clinical trials but stopped work on the small molecule in 2019. According to Acrivon’s prospectus, Lilly’s Phase 2 tests in ovarian cancer led to an overall response rate of just 12%. Acrivon believes that by identifying likely responders, its technology can lead to better response rates.
Acrivon was able to obtain pretreatment samples from a subset of ovarian cancer patients who participated in prexasertib trials run by the National Cancer Institute (NCI) and Lilly. According to the IPO filing, a third-party biostatistician reviewed the trial data and OncoSignature scores and found that using the Acrivon test to identify patients appropriate for the therapy boosted the response rate to 47% in the NCI trial 58% in the Lilly study. Acrivon also said the analysis was able to eliminate patients who are less responsive to the drug, which would have spared them from a treatment that would not help them.
Acrivon plans to advance ACR-368 into single-arm Phase 2 studies in ovarian, endometrial, and bladder cancers. Participants in the trials, which the company said could support potential regulatory submissions, will be assigned to subgroups according to their sensitivity to the test drug as determined by OncoSignature.
Acrivon acquired prexasertib in 2021 for cheap. According to the IPO filing, the biotech paid $5 million in cash and issued Lilly shares in the company. Acrivon could pay Lilly up to $168 million in milestone payments linked to the progress of the drug, plus royalties from sales if it reaches the market. The agreement also gives Lilly limited first rights to negotiate the reacquisition of the cancer drug. That right expires 45 days after the completion of certain clinical milestones that are not specified in the IPO filing.
While ACR-368 gives Acrivon an asset ready for a new slate of mid-stage tests, its preclinical programs address other pathways key to DNA damage response. One addresses a protein called WEE1; the other a protein called PKMYT1. There are competitors developing drugs that address DNA damage response. GSK acquired Sierra Oncology largely due to the promise of myelofibrosis drug momelotinib, but that biotech’s pipeline also includes CHK1 inhibitor SRA737. Phase 2 work on adavosertib, a WEE1-blocking small molecule that AstraZeneca licensed from Merck, was stopped this past summer. But others that have reached the clinic with WEE1 inhibitors include Zentalis Pharmaceuticals, Debiopharm, and Impact Pharmaceuticals.
Acrivon’s stock market debut comes nearly one year after it raised $100 million in Series B financing. Prior to the IPO, the biotech raised $119.8 million, according to the filing. Chione is Acrivon’s largest shareholder, owning 18.4% of the company after the IPO. RA Capital Management owns a 7.5% stake. Acrivon reported its cash position was $83.9 million at the end of June. Most of the IPO cash will go toward development of ACR-368. Between $80 million and $90 million is planned for defining the manufacturing processes and product specifications of the drug as well as developing a companion diagnostic, according to the filing.
In time, Acrivon plans to test ACR-368 in other cancers based on drug sensitivity assessed by OncoSignature. Those cancers include human papilloma virus positive squamous cell cancer of the head and neck, as well as anal and cervical cancers. The IPO filing states that the company plans to use some of the new capital to start a mid-stage test in patients with HPV-positive tumors. Another $15 million to $20 million is set aside for completing the preclinical testing leading up to an investigational new drug application for at least one of the company’s preclinical programs. The company will use the remaining cash to continue development of the AP3 technology and for other R&D work. Acrivon expects the cash to support the company into the fourth quarter of 2024.
Photo by Flickr user FutUndBeidl via a Creative Commons license
