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Acrivon (NASDAQ:ACRV) develops precision cancer medicines and then uses its proprietary proteomics-based patient responder identification platform, Acrivon Predictive Precision Proteomics, or AP3, to match patients whose tumors are sensitive to that medicine. This leads to a drug-specific companion diagnostics called OncoSignature. Lead candidate is ACR-368, a selective small molecule inhibitor targeting CHK1 and CHK2. ACR-368 is currently in a potentially registrational Phase 2 trial across multiple tumor types. Other programs are preclinical.
ACR-368 has been licensed from Eli Lilly & Co. (LLY) in an all-equity deal. It is a clinically active phase 2 Damage Response (DDR) inhibitor with a tested 15-20% ORR. Acrivon’s goal is to use its OncoSignature diagnostic and patient selection platform to improve these ORR figures. They are running a phase 2 trial with an intent to convert this to a registrational trial if possible. There are phase 2 trials in Platinum-Resistant Ovarian Cancer, Endometrial Cancer, Bladder Cancer and HPV+ SCC (anal, H&N and cervical cancer) for ACR-368 monotherapy in OncoSignature-positive patients. There are exploratory phase 1b/2 single arm trials of ACR-368 in combination with low dose gemcitabine, or LDG, in OncoSignature-negative patients.
Acrivon is a recent IPO launched last November amidst some of the worst periods in biotech, forever to be known as the biotech winter. ACR-368 originates in research done since 2001 in a collaboration between Array Biopharma and Icos, where it was known as prexasertib. After Lilly acquired Icos, and Pfizer (PFE) acquired Array, Lilly continued with its trials of prexasertib, just as Roche continued trials of another CHK-1 inhibitor, RG7741, which also began life at Array. Trials saw ORR of 15-20%, but Roche discontinued work with RG7741 in 2018, and Lilly followed a year later.
Drug activity was observed in some 30% of ovarian cancer patients sensitive to prexasertib, however the ORR, as we can see, was relatively poor. According to Acrivon, “29% at the single center Phase 2 ovarian cancer trial at NCI in the intent to treat, or ITT, population, and approximately 12% across the platinum-resistant ovarian cancer cohorts in the large Phase 2 multi-center international trial sponsored by Lilly.” Acrivon’s idea is to use this old molecule with its OncoSignature platform and try to identify patients in whom the ORR rate can be improved. Data is supposed to come in mid-2023. However, it is important to remember that prexasertib will have no real patent protection, and the only protection we can expect is through a mix of method and via Oncosignature patents.
The idea is interesting, and potentially doable. A lot of promising drugs fail in phase 2 trials because patients are selected by indication and prior treatment modalities and so on, and not through whether they are sensitive to the tested medicine. Nowadays, patients are tested for certain genetic situations, like if they have a BRAF mutation, and given precision drugs that address those mutations. Acrivon is extending that concept beyond genetics, and using their proprietary testing methodology, they are testing patients before they join the trial. If the patient is sensitive to the test, they are included; if not, they are excluded. This, according to the CEO, is, among other things, a way to avoid overtreatment in these late stage patients, as well as to improve trial results by only including those patients who have a higher possibility of responding to the tested drug.
Not a lot of details are available about the AP3 platform. In their S1, the company states:
Our ACR-368 OncoSignature test, which has not yet obtained regulatory approval, has been extensively evaluated in preclinical studies, including in two separate, blinded, prospectively-designed studies on pretreatment tumor biopsies collected from patients with ovarian cancer treated with ACR-368 in past Phase 2 clinical trials conducted by Eli Lilly and Company, or Lilly, and at the National Cancer Institute, or NCI, demonstrating robust enrichment of responders through our method.
So while this does not divulge precisely how AP3 works, including what the 3 biomarkers are for selecting patient responders, it tells us that the platform was tested on ACR-368 thoroughly, and found to be useful, in preclinical and other model studies. Because ACR-368 has been tested in over 400 patients, has seen durable responses including CRs, and has been generally well-tolerated, the company was able to jump directly into a potentially registrational phase 2 trial with the FDA’s blessings.
The company also used its platform to identify resistance mechanisms in certain tumors. The company discovered that low dose gemcitabine can overcome some of these resistances and further sensitize these tumors to ACR-368 by inducing increased DDR stress. The company will incorporate these ideas into further trials in OncoSignature-negative patients.
Financials
ACRV, a recent IPO, has a market cap of $273mn, a stock price of $13, and a cash reserve of $170mn. There are financial statements from September 2022 – here – where cash shown is some $77mn. To this has been added the IPO funds, and we have the $170mn as of December 2022. R&D/G&A are from before the IPO, and these are $8mn and $2mn approximately and respectively. However, these figures are not reliable because the company will soon launch a phase 2 trial and will also have considerable other costs. The company guides for a cash runway till Q4 2024, so we will have to go with that.
The stock went up 30% post IPO, but between February and March 7, it plunged back down 30% on very high volume on a single day. There was no news. It will probably turn out to be the sound of early investors leaving.
Bottomline
The company is interesting, and everything is predicated on the AP3 platform thing about which we know very little. The company has chosen not to divulge. They have patent coverage for the platform, and some coverage from the unlicensed molecule as well. Their cash balance is okay but will need replenishing. Their logic is sound – somebody needs to make clinical trials more efficient – however we need to really wait a lot longer before we see some validation of their claims. As is my usual style, I will choose not to get excited too early.
