Chondrial Sets Up Rare Disease Shop With In-Licensed Asset, Series A 

By Marie Powers, News Editor

Three-year-old Chondrial Therapeutics Inc. scored a series A financing of up to $22.6 million and licensed its first asset in a quest to build a pipeline of therapies to treat rare mitochondrial diseases. The financing was led by Deerfield Management. Pharma veteran and former Deerfield adviser Carole Ben-Maimon was named Chondrial’s president and CEO. 

The company’s lead candidate, CTI- 1601, was discovered by Chondrial co-founder R. Mark Payne, professor of pediatric cardiology at Indiana University School of Medicine and director of the Translational Research Training Program of Indiana Clinical Translational Sciences Institute, while he was a scientist at Wake Forest Baptist Medical Center. The asset, targeting Friedreich’s ataxia (FA), was licensed from Indiana University Research and Technology Corp. and Wake Forest University Health Sciences. The Catalyst Fund, a $15 million technology development program of Wake Forest Innovations managed by Pappas Capital, was a minority participant in the A round. 

Chondrial, of Bala Cynwyd, Pa., was founded in 2013 by Payne and Steven Plump, a former official at Indianapolis-based Eli Lilly and Co. A year later, the company collected seed financing of about $1.6 million, according to SEC documents. Thomas Hamilton, a member of the board at the Friedreich’s Ataxia Research Alliance, was the company’s initial sole investor, Ben- Maimon said. 

Early on, Chondrial began working to scale up manufacturing, while board member Hamilton, who had a longstanding relationship with Deerfield, brought the asset to the venture firm’s attention. Serendipitously, in 2015 Deerfield established a $550 million fund targeting early stage science from academic research institutions, with a focus on advancing therapies targeting genetic disorders, cancer and orphan diseases into the clinic. 

Deerfield first asked Ben-Maimon, who was consulting with the venture firm at the time, to conduct due diligence on Chondrial and, later, to step in as CEO. Ben-Maimon previously served as president of Global Pharmaceuticals, the generics unit of Impax Laboratories Inc., and had earlier roles at Barr Pharmaceuticals Inc. and, after its acquisition, by parent Teva Pharmaceutical Industries Ltd. 

“That’s what I love to do – start small companies and develop drugs, so it was a good fit,” Ben-Maimon told BioWorld Today


FA, which occurs in about one in 5,000 people in the U.S. and about twice that number in Europe, is caused by an abnormality in the FXN gene, inherited in autosomal recessive fashion, that is responsible for the production of frataxin. Although the function of frataxin isn’t clearly understood, the protein is known to be active in the mitochondria and to assist with energy production. Individuals with FA have very low levels of frataxin, resulting in the debilitating condition. 

CTI-1601 uses a carrier protein to deliver frataxin, typically produced elsewhere in the cell, to the mitochondria. Chondrial’s research premise is that, by replacing the deficient protein, the mitochondria will resume normal function, resulting in a lessening of symptoms and slowing or curtailment of disease progression. 

“It’s a real challenge to get drugs or proteins of any kind through the extracellular membrane, then through the mitochondrial membrane, and then get them to stay,” Ben- Maimon explained. The carrier protein that Payne selected “worked quite effectively,” she said, solving the transport problem and enabling the protein to “stick” inside the mitochondria. 

The company’s therapeutic hypothesis remains to be proved, Ben-Maimon acknowledged, but she’s confident that Payne’s decades of research in the mitochondrial space stand the company in good stead to advance CTI-1601 into the clinic. Chondrial is completing preclinical work on the asset and plans to initiate a pre-investigational new drug (IND) application meeting with the FDA this year. Based on the agency’s guidance, the company will complete manufacturing and IND-enabling studies before filing an IND application as quickly as possible. 

“Knowing the population of patients that we’re dealing with, the faster we go, the happier we’ll all be,” Ben-Maimon said. “It’s a very bad disease, and it’s progressive. We’re hopeful it’s reversible in the early stages, but we don’t know when that changes so we’re very anxious to get moving. This is our highest priority.” 

FA remains a rare disease space in search of therapeutic options. Patients suffered a crushing blow in December when Horizon Pharma plc, of Dublin, reported the failure of its phase III STEADFAST (Safety, Tolerability and Efficacy of Actimmune Dose Escalation in Friedreich’s Ataxia study), which missed the primary and secondary endpoints in evaluating Actimmune (interferon gamma-1b) to treat FA. (See BioWorld Today, Dec. 9, 2016.) 

Actimmune was the only agent in an active phase III program, according to Cortellis Clinical Trials Intelligence (CTI), so its failure appeared to propel a phase II FA asset to the head of the class. Reata Pharmaceuticals Inc. is advancing omaveloxolone, a close structural analogue of bardoxolone methyl that was developed to improve tissue distribution, in the randomized, placebo-controlled study known as MOXIE, with initial data expected in the first half of this year. (See BioWorld Today, May 27, 2016.) 

Edison Pharmaceuticals Inc. also has a phase II asset, EPI-743, an orally bioavailable small molecule that’s a member of the para-benzoquinone drug class targeting the enzyme NADPH quinone oxidoreductase 1. The drug completed a phase IIb trial in FA, and in 2013 privately held Edison inked an R&D and commercialization agreement with Dainippon Sumitomo Pharma Co. Ltd. to advance the lead program EPI-743 in Japan, but the companies have not disclosed additional development, according to Cortellis CTI. (See BioWorld Today, March 29, 2013.) 

The richer FA pipeline is upstream. In all, 17 of 24 disclosed drugs actively targeting FA have yet to move into the clinic, according to CTI. They include assets from established companies such as Biomarin Pharmaceutical Inc., Bioblast Pharma Ltd., Proqr Therapeutics BV and Rana Therapeutics Inc. Newer entrants, in addition to Chondrial, include Agilis Biotherapeutics LLC, Fratagene Therapeutics Ltd. and Voyager Therapeutics Inc., which has a potential $845 million deal with Sanofi SA’s Genzyme unit to pursue treatments for FA and other central nervous system diseases. (See BioWorld Today, Jan. 2, 2014, Aug. 18, 2014, and Feb. 12, 2015.) 

Another company with FA in its sights, Bamboo Therapeutics Inc., was acquired last year by New York-based Pfizer Inc. for $150 million up front and milestone payments of up to $495 million. (See BioWorld Today, Aug. 2, 2016.) 

Chondrial’s series A is designed primarily to advance FA-1601 into a phase I program in FA, but the four-person company also is ramping up R&D efforts in other rare mitochondrial diseases at a newly established laboratory at the Science Center in Philadelphia. 

“We are looking at other assets that target mitochondrial diseases, and we think Deerfield will support that,” Ben- Maimon confirmed. Payne, as chief scientific officer, and Plump, as executive advisor, remain important members of the R&D team, she added. 

Longer term, “we’ll be opportunistic,” Ben-Maimon said. “We definitely want to take CTI-1601 at least through phase I, which will be more than just a safety and tolerability study. We’ll also be looking at some pharmacodynamics in patients. Once we’re comfortable that we have proof of concept that shows this is a viable treatment for Friedreich’s, we’ll move aggressively.”