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Acrivon Nets $100M for Protein Tech That Picks Patients for Targeted Cancer Meds – MedCity News


For focused most cancers remedy to work, it’s not sufficient to determine the precise targets to hit with a drug. Simply as necessary is deciding on the sufferers acceptable for a given remedy. Scientists at Acrivon Therapeutics say their method 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 technique to increase almost $100 million for its scientific trial plans.

Acrivon got here near the nine-figure IPO it needed, nevertheless it needed to slash the inventory value and promote extra shares in an effort 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 putting 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 beneath the inventory image “ACRV.”

Matching a most cancers drug to a affected person is often completed in keeping with 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. Quite than on the lookout for a genetic goal, Acrivon measures proteins which might be vital to tumor-driving mechanisms. The corporate contends this proteomics method might be relevant to nearly all of cancers that do not need 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 mentioned in its up to date prospectus.

The science upon which Acrivon’s know-how relies stems from the analysis of co-founder and CEO Peter Blume-Jensen, whose pharma business expertise consists of senior roles at EMD Serono and Merck & Co. In a 2001 article revealed within the journal Nature, Blume-Jensen and co-author Tony Hunter describe how most cancers is pushed by dysregulated protein signaling.

Acrivon, whose title is derived from the Greek phrase for “correct,” fashioned in 2018. The corporate’s tech platform, referred to as Acrivon Predictive Precision Proteomics, or AP3, develops tumor biopsy checks that can be utilized to match a drug to the sufferers probably to reply to it. These checks, referred to as OncoSignature, measure for elevated ranges of proteins {that a} tumor will depend 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 scientific trial, the biotech turned to a molecule that stalled within the fingers of Eli Lilly.

The Lilly drug, prexasertib, has an extended historical past with a number of stops. Initially developed beneath 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 guts 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 manner tumors repair themselves. The fast and uncontrollable cell progress 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 briefly cease cell replication in an effort to permit restore of DNA injury. Blocking these proteins prevents these repairs, main as an alternative to cell demise.

No CHK1/2 inhibitors have been authorized by the FDA but. Lilly superior its CHK1/2-blocking drug to a number of Part 1 and Part 2 scientific trials however stopped work on the small molecule in 2019. In response to 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 seemingly responders, its know-how can result in higher response charges.

Acrivon was capable of get hold of 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. In response to the IPO submitting, a third-party biostatistician reviewed the trial knowledge and OncoSignature scores and located that utilizing the Acrivon check to determine sufferers acceptable for the remedy boosted the response charge to 47% within the NCI trial 58% within the Lilly examine. Acrivon additionally mentioned the evaluation was capable of remove sufferers who’re much less attentive to the drug, which might have spared them from a remedy that might 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 mentioned might help potential regulatory submissions, shall be assigned to subgroups in keeping with their sensitivity to the check drug as decided by OncoSignature.

Acrivon acquired prexasertib in 2021 for reasonable. In response to 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 provides Lilly restricted first rights to barter the reacquisition of the most cancers drug. That proper expires 45 days after the completion of sure scientific milestones that aren’t specified within the IPO submitting.

Whereas ACR-368 provides Acrivon an asset prepared for a brand new slate of mid-stage checks, its preclinical packages handle different pathways key to DNA injury response. One addresses a protein referred to as WEE1; the opposite a protein referred to as PKMYT1. There are opponents creating medicine that handle 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 embody Zentalis Prescription drugs, Debiopharm, and Impression Prescription drugs.

Acrivon’s inventory market debut comes almost one yr after it raised $100 million in Sequence B financing. Previous to the IPO, the biotech raised $119.8 million, in keeping with 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. Many of the IPO money will go towards improvement 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, in keeping with the submitting.

In time, Acrivon plans to check ACR-368 in different cancers primarily based on drug sensitivity assessed by OncoSignature. These cancers embody human papilloma virus optimistic 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 start out 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 software for not less than one of many firm’s preclinical packages. The corporate will use the remaining money to proceed improvement of the AP3 know-how and for different R&D work. Acrivon expects the money to help the corporate into the fourth quarter of 2024.

Picture by Flickr consumer FutUndBeidl by way of a Artistic Commons license


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