Coherent Biopharma, WuXi STA Collab Takes a Crack at Peptide-Drug Conjugates

Antibody-drug conjugates (ADCs) dominate the spotlight for targeted cancer therapies, but are limited by poor tumor penetration as antibodies are pretty big (~150 kDa) by molecular standards. Moreover, they’re expensive to produce and carry additional risks such as stimulating undesirable immune responses and toxicity. In recent years, peptide-drug conjugates (PDC) have gained increasing attention as the next big thing in targeted therapy due to their smaller sizes, favorable safety profile and superior ability to diffuse into malignant tissue. 

Coherent Biopharma is one of those companies working to bring PDCs into the mainstream of cancer treatments. Last month, the Suzhou-based company reached out to WuXi SynTheAll Pharmaceutical (WuXi STA), a CDMO owned by WuXi AppTec, to develop PDCs. 

Under the deal, WuXi STA will become Coherent’s “preferred CDMO partner”, providing services from drug development and manufacturing to analytical support and regulatory filing. Besides peptides, WuXi STA could also help Coherent develop small molecules, oligonucleotides and complex chemical conjugates. 

The collaboration is expected to accelerate development of Coherent’s drug candidates. Two of them, CBP-1008 and CBP-1018, are in clinical trials in the US and China. Coherent hints that more drugs are in the works, and they will be ready for clinical development in a few years. 

“Coherent is one of the pioneers in the development of PDC drugs in China and has made great progress,” said Dr. Minzhang Chen, CEO of WuXi STA. “We are looking forward to further leveraging our proven integrated CMC (Chemistry, Manufacturing and Controls) platform, along with our global standard quality systems, to accelerate Coherent’s innovative drug development and ultimately benefit global patients.”

Related Article: New Frontiers in Therapeutics

PDCs in Cancer and ex-Cancer Applications 

PDCs are composed of a peptide, a drug payload, and a biodegradable linker. The peptide homes in on biomarkers to deliver its drug payload at a specific location. In the case of cancer, peptides targeting cancer biomarkers could deliver anticancer drugs into the cells to specifically kill them while minimizing damage to healthy cells. 

Coherent believes that PDCs are scalable, able to penetrate tumors, and possess good pharmacokinetics. Its lead candidate, CBP-1008, has been investigated in a Phase 1a trial in patients with advanced malignant solid tumors who have failed multiple treatments. In the trial, the drug demonstrated antitumor activity, reduced target lesions and had a manageable safety profile. 

Coherent expects to test CBP-1008 against gynecological, gastrointestinal and breast tumors. The other lead candidate, CBP-1018, is being investigated for metastatic and recurrent solid tumors that affect the lungs and urinary system. 

PDCs look promising on paper, but they are still an emerging therapeutic field. The first FDA approval for an anticancer PDC was given in February 2021 to Pepaxto (melphalan flufenamide), which was developed by Swedish biotech Oncopeptides AB as a last resort for multiple myeloma. Despite receiving accelerated approval, Oncopeptides had to pull Pepaxto from the US market in October after the FDA ruled that its confirmatory Phase 3 Ocean study did not meet safety standards.  

Beyond cancer, companies are also looking into PDCs as treatments for other diseases.

A recent multi-billion dollar collaboration between Takeda and PeptiDream seeks to combine the former’s compounds with the latter’s transferrin receptor binding peptide (carrier peptide) to create PDCs for neuromuscular diseases.  

Meanwhile, PepGen is conjugating peptides with a therapeutic oligonucleotide to create a PDC that could treat myotonic dystrophy type 1, a progressive muscle disease. The PDC targets exon 51, stimulating exon-skipping to produce a functional protein which restores function to muscle cells. 

Related Article: Ablaze Pharma Launches with $75 Million to Bring Targeted Radiotherapies into China 

Author

Joy Lin

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