In its second acquisition of the past four weeks, Lodo Therapeutics Corp., acquired Hibiskus Biopharma Inc. plus exclusive worldwide rights from the University of California Riverside and Michigan State University to preclinical proteasome and immunoproteasome inhibitors developed by Hibiskus’ two co-founders.

On Aug. 7, Lodo completed the acquisition of Doylestown, Pa.-based Conifer Point Pharmaceuticals LLC, which has proprietary tools and expertise in computational structural biology and cheminformatics. Lodo said it plans to integrate Conifer Point's technology and know-how to enhance its artificial intelligence/machine learning capabilities and expand its P4 Platform for the in-silico discovery of novel drug leads from biosynthetic gene clusters in microbial DNA.

The path to Lodo’s acquisition of Hibiskus stretches back 25 years to Palo Alto, Calif., when Lodo CEO Dale Pfost and Hibiskus co-founder Michael Pirrung, now a University of California Riverside professor and drug researcher, first met. “Relationships matter,” Pfost told Bioworld.

“He’s very disciplined. He’s a renaissance guy,” Pfost added. “He was at Stanford doing light-activated chemistry 25 years ago.”

Dale Pfost, CEO, Lodo

Pfost invited Pirrung to join Lodo’s scientific advisory board and the two began comparing notes in an effort to take Hibiskus to the next stage, which led to the acquisition. Michigan State University’s André Bachmann, a cancer researcher, is Hibiskus’ other co-founder.

Hibiskus’ lead preclinical molecule, the newly renamed LODO-141, a small-molecule cancer therapy in development, is an irreversible and hybrid cyclic peptide proteasome inhibitor from the syrbactin natural product family. Preclinical studies conducted at the U.S. National Cancer Institute suggest the small molecule may have utility in treating a number of solid tumors. Pfost said Lodo plans to assess LODO-141 as a single agent and also in combination with cancer immunotherapy.

Preclinical data published in the Journal of Biological Chemistry showed LODO-141 had antiproliferative activity in human solid tumor cell lines that include renal, colon, non-small-cell lung, melanoma, ovarian, prostate and breast cancers. The research showing in vivo efficacy supporting the company’s plans to advance it for treating solid tumors and perhaps some other cancers was found in a multiple myeloma xenograft model and hollow fiber models of solid tumor carcinomas.

Other preclinical data, published in Leukemia Research, showed LODO-141 was effective in resistant multiple myeloma and mantle cell lymphoma.

“It’s a natural product,” Pfost added. “It will get benefit from our platform.”

Lodo has what Pfost calls “a fantastic suite of biologies” with a repertoire of dovetailed technologies that takes a DNA-first approach in understanding drug-like molecules encoded in microbial DNA. The payoff, he continued, is tapping into this new chemical space, something he described as “not your grandfather’s molecular library. … It’s revolutionary.”

The platform “opens access to the largest reservoir of chemically diverse molecules known to humanity and they all have biological relevance,” he added.

The company plans to take all of Hibiskus’ operating assets and consolidate them in New York.

Partnerships are central to the way New York-based Lodo conducts business, using its platform as the centerpiece. The company hit a preclinical milestone in April with its Genentech Inc. collaboration by using its genome mining and biosynthetic cluster assembly platform to identify molecules with therapeutic potential against multiple disease-related targets of interest to Genentech. In the collaboration, Lodo’s platform makes bioactive natural products directly from the microbial DNA sequence information contained in soil. In the multitarget collaboration, Genentech could contribute nearly $1 billion in up-front, research, development and commercialization milestone payments, along with tiered royalties on sales.

The partnerships have been rewarding for Lodo, Pfost said: “Those two programs allowed us to get this platform up and running.”

Lodo launched in January 2016 from the New York arm of Accelerator Corp. with the help of a $17 million series A. The Bill and Melinda Gates Foundation was an early investor.

Lodo has been rearranging itself for a few months. Pfost was appointed CEO and chairman of the board in December 2019. Most recently, in early July, the company appointed Steve Colletti as chief scientific officer and Brad Hover as vice president of discovery research and platform technology. At the same time, Pirrung, Sean Brady, Jon Clardy, Benjamin Cravatt, Peter Karp and Christine Schuberth-Wagner were added to the scientific advisory board.

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