For focused most cancers remedy to work, it’s not sufficient to establish the suitable targets to hit with a drug. Simply as essential is choosing the sufferers acceptable for a given remedy. Scientists at Acrivon Therapeutics say their strategy brings benefits over genetic-based affected person choice. The Acrivon know-how is approaching its first checks in people with a drug acquired from an enormous pharmaceutical firm. The IPO market, just like the climate, has turned chilly however Acrivon nonetheless discovered a solution to increase practically $100 million for its medical trial plans.
Acrivon got here near the nine-figure IPO it wished, nevertheless it needed to slash the inventory value and promote extra shares so as to pull it off. This previous week, the biotech supplied greater than 7.5 million shares for $12.50 apiece, which raised $94.4 million. When Acrivon set preliminary phrases for the IPO earlier this month, it deliberate to supply 5.9 million shares priced within the vary of $16 to $18 every.
Watertown, Massachusetts-based Acrivon was capable of get nearer to the $100 million mark by hanging a separate and concurrent deal. Chione Restricted, the most important shareholder within the firm previous to the IPO, bought 400,000 shares on the IPO value, elevating one other $5 million. Acrivon shares now commerce on the Nasdaq underneath the inventory image “ACRV.”
Matching a most cancers drug to a affected person is often carried out based on genomics. That works when tumors have single driver mutation that causes cells to change into cancerous. However Acrivon notes that greater than 90% of all human cancers don’t have such mutations. Somewhat than searching for a genetic goal, Acrivon measures proteins which might be important to tumor-driving mechanisms. The corporate contends this proteomics strategy may very well be relevant to the vast majority of cancers that don’t have genetic alterations within the drug goal itself.
“Our founding imaginative and prescient is that proteomic biomarkers allow direct measurement of the disease-driving mechanisms and permit for correct matching with drug motion, unbiased of underlying genetic alterations,” Acrivon stated in its up to date prospectus.
The science upon which Acrivon’s know-how is predicated stems from the analysis of co-founder and CEO Peter Blume-Jensen, whose pharma trade expertise consists of senior roles at EMD Serono and Merck & Co. In a 2001 article printed within the journal Nature, Blume-Jensen and co-author Tony Hunter describe how most cancers is pushed by dysregulated protein signaling.
Acrivon, whose identify is derived from the Greek phrase for “correct,” shaped in 2018. The corporate’s tech platform, known as Acrivon Predictive Precision Proteomics, or AP3, develops tumor biopsy checks that can be utilized to match a drug to the sufferers almost certainly to answer it. These checks, known as OncoSignature, measure for elevated ranges of proteins {that a} tumor relies on and which might be particular to biochemical pathways addressed by a drug. Acrivon has used OncoSignature to information the event of internally found drug candidates which might be presently preclinical. For OncoSignature’s first check in a medical trial, the biotech turned to molecule that stalled within the arms of Eli Lilly.
The Lilly drug, prexasertib, has a protracted historical past with a number of stops. Initially developed underneath a collaboration between Array Biopharma and Icos, the drug joined Lilly by way of the pharma large’s $2.1 billion acquisition of Icos in 2007. The center of that deal was blockbuster erectile dysfunction drug Cialis; prexasertib was nonetheless preclinical on the time.
Prexasertib is designed to deal with most cancers by interfering with a means tumors repair themselves. The fast and uncontrollable cell development attribute of most cancers wreaks havoc on most cancers DNA. Tumors depend on DNA injury response, a restore mechanism ruled by sure proteins. The Lilly drug, which Acrivon has renamed ACR-368, is designed to dam CHK1 and CHK2, two proteins that quickly cease cell replication so as to enable restore of DNA injury. Blocking these proteins prevents these repairs, main as an alternative to cell demise.
No CHK1/2 inhibitors have been permitted by the FDA but. Lilly superior its CHK1/2-blocking drug to a number of Part 1 and Part 2 medical trials however stopped work on the small molecule in 2019. Based on Acrivon’s prospectus, Lilly’s Part 2 checks in ovarian most cancers led to an general response charge of simply 12%. Acrivon believes that by figuring out possible responders, its know-how can result in higher response charges.
Acrivon was capable of acquire pretreatment samples from a subset of ovarian most cancers sufferers who participated in prexasertib trials run by the Nationwide Most cancers Institute (NCI) and Lilly. Based on the IPO submitting, a third-party biostatistician reviewed the trial knowledge and OncoSignature scores and located that utilizing the Acrivon check to establish sufferers acceptable for the remedy boosted the response charge to 47% within the NCI trial 58% within the Lilly research. Acrivon additionally stated the evaluation was capable of eradicate sufferers who’re much less conscious of the drug, which might have spared them from a therapy that will not assist them.
Acrivon plans to advance ACR-368 into single-arm Part 2 research in ovarian, endometrial, and bladder cancers. Individuals within the trials, which the corporate stated might assist potential regulatory submissions, will probably be assigned to subgroups based on their sensitivity to the check drug as decided by OncoSignature.
Acrivon acquired prexasertib in 2021 for affordable. Based on the IPO submitting, the biotech paid $5 million in money and issued Lilly shares within the firm. Acrivon might pay Lilly as much as $168 million in milestone funds linked to the progress of the drug, plus royalties from gross sales if it reaches the market. The settlement additionally offers Lilly restricted first rights to barter the reacquisition of the most cancers drug. That proper expires 45 days after the completion of sure medical milestones that aren’t specified within the IPO submitting.
Whereas ACR-368 offers Acrivon an asset prepared for a brand new slate of mid-stage checks, its preclinical applications tackle different pathways key to DNA injury response. One addresses a protein known as WEE1; the opposite a protein known as PKMYT1. There are opponents creating medicine that tackle DNA injury response. GSK acquired Sierra Oncology largely as a result of promise of myelofibrosis drug momelotinib, however that biotech’s pipeline additionally consists of CHK1 inhibitor SRA737. Part 2 work on adavosertib, a WEE1-blocking small molecule that AstraZeneca licensed from Merck, was stopped this previous summer season. However others which have reached the clinic with WEE1 inhibitors embrace Zentalis Prescription drugs, Debiopharm, and Impression Prescription drugs.
Acrivon’s inventory market debut comes practically one 12 months after it raised $100 million in Collection B financing. Previous to the IPO, the biotech raised $119.8 million, based on the submitting. Chione is Acrivon’s largest shareholder, proudly owning 18.4% of the corporate after the IPO. RA Capital Administration owns a 7.5% stake. Acrivon reported its money place was $83.9 million on the finish of June. A lot of the IPO money will go towards growth of ACR-368. Between $80 million and $90 million is deliberate for outlining the manufacturing processes and product specs of the drug in addition to creating a companion diagnostic, based on the submitting.
In time, Acrivon plans to check ACR-368 in different cancers primarily based on drug sensitivity assessed by OncoSignature. These cancers embrace human papilloma virus constructive squamous cell most cancers of the pinnacle and neck, in addition to anal and cervical cancers. The IPO submitting states that the corporate plans to make use of among the new capital to begin a mid-stage check in sufferers with HPV-positive tumors. One other $15 million to $20 million is put aside for finishing the preclinical testing main as much as an investigational new drug utility for at the least one of many firm’s preclinical applications. The corporate will use the remaining money to proceed growth of the AP3 know-how and for different R&D work. Acrivon expects the money to assist the corporate into the fourth quarter of 2024.
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