Perpetual aims to be peptide powerhouse

The field of peptides is exploding, Perpetual Medicines Corp. co-founder, chairman and CEO Kerry L. Blanchard recently told BioWorld, “with a projected growth rate far surpassing large and small molecules, and gene therapies. The area is underinvested, too, so this is a good opportunity to focus on peptide therapeutics.”

Blanchard, who was most recently CEO of Shanghai-based Everest Medicines Ltd. and previous chief scientific officer (CSO) of China’s Innovent Biologics Co. Ltd., is now spearheading efforts to develop novel peptide therapeutics at his own biotech, Perpetual, founded in March 2023.

Peptide therapeutics is considered one of the most rapidly growing pharmaceutical sectors, Blanchard said, and its growth is expected to surpass $140 billion annually, aided by the advances in computational technology and artificial intelligence (AI), which have driven modern drug discovery.

Operating out of Shanghai but with scientists stationed across the U.S., Perpetual raised $8 million in seed financing in November 2023. The funding round, led by Chengwei Capital, will help both accelerate Perpetual’s most advanced program to the clinical stage and build its preclinical portfolio in oncology, autoimmunity and metabolic diseases.

In the pipeline are three major oncology projects that, while not named, “are all intracellular targets” – an area where Blanchard sees peptides as the best-suited modality to interrupt protein-protein interactions (PPI), which has been difficult with small molecules.

Perpetual, as a 9-person biotech, employs its integrated computation design and synthesis platform for peptide drug discovery that capitalizes “on the recent advances in computational modeling based on AI, deep learning and machine learning.”

Notably, the progress of recombinant peptides and AI have enabled, “for the first time, access to the enormous, untapped peptide chemical space for drug discovery,” according to Blanchard.

Perpetual’s self-developed integrated platform will help its scientific team sift through millions of peptide sequences using physics-based computations and predict binding and drug-like properties. The firm will combine these discovery efforts with experimental data to develop new drugs.

From Lilly, Innovent, Everest to Perpetual

As a U.S. physician trained at Harvard Medical School, Blanchard was primarily an academic physician scientist before working up to an executive role at Eli Lilly and Co., including at Lilly’s China branch where he worked for 8 years.

Lilly was where Blanchard grew into the field of peptide drugs, especially for metabolic diseases.

The American pharma giant was the first to win approval for Mounjaro (tirzepatide) for type 2 diabetes as a GLP-1/GIP dual agonist in May 2022. Lilly also gained FDA approval for the same drug as Zepbound (tirzepatide) for chronic weight management for obesity patients in November 2023. In the PPI drug space, Lilly advanced a $2.4 billion deal to acquire Dice Therapeutics Inc. and its technology platform, Delscape, in July 2023 to discover selective oral small molecules that can modulate PPIs.

After Lilly, Blanchard moved to the Suzhou- and Shanghai-based Innovent, taking on the role of CSO. There, he helped build up the Chinese startup biotech founded in 2011 and played a key role in Innovent’s IPO on the Hong Kong stock exchange (HKEX) in 2018.

“After Innovent became a commercial company, I moved to Everest – a Shanghai-based licensing company founded in 2017,” Blanchard said. “I also took Everest through its series C funding, IPO and first drug approval, but they, again, became a commercial company – and I’m not a commercial guy.”

Blanchard served as CEO of Everest from February 2020, helping the company list on the HKEX in October 2020. He stepped down in June 2022.

“I wanted to get back to where I spent a lot of my life: in discovery, and in early basic research – where my love is.”

Now Blanchard, at 68 years of age – with Ved Srivastava as chief technology officer and Xiang Ye as chief scientific officer – wants Perpetual to focus solely on peptide therapeutics, which could become “the biggest drugs in the history of the world.”

While Blanchard was “never big” on focusing on a single modality (like antibodies, small or large molecules, peptides and so on), he saw the potential of peptide drugs like Eli Lilly and Co.’s Mounjaro – forecasted by some analysts to become “the first drug to reach the $100 billion-a-year-club.”

Peptide therapeutics have indeed come a long way, he said. Initially, they were mined from animal organs, from nature, whether calcitonin from salmon or insulin from pigs’ pancreases: “Nature made it, and we just purified it to a point it could be used in humans.” But peptide synthesis drastically improved, and by the 1980s, recombinant technology ushered in a new era of recombinant peptides.

“In the last several years,” Blanchard stressed, “there were tremendous advances in deep learning and machine learning with Deepmind’s Alphafold, which allowed us to go from protein sequence to structure computationally – and be right most of the time.”

The combined advances across the three areas of the peptide market, recombinant and synthetic peptides and computational models are now advancing the fourth renaissance of peptide therapeutics: “The first [renaissance] was isolating peptides from animals; the second was to produce them synthetically; the third was recombinant technology; and now the fourth comes with advanced computational power and capabilities.”

Perpetual is now seeking to capitalize on the gains of peptide therapeutics in its fourth renaissance. The plan is to virtually design peptide structures and “sample the huge peptide chemical space through virtual approaches and then use physics-based methods to predict binding affinity.”

Partnerships in virtual AI will also help accelerate progress considering “we need to start generating data on large sets of peptides. That’s going to take more than one company – nobody can do it themselves.”

While the biotech is still in its infancy, the plan is to move forward its AI-driven drug discovery and development for peptide therapeutics. If successful, Blanchard said, the drug development process will roll onwards like a perpetual motion machine – an ideal device that moves continually, once set in motion.