Reneo: Small molecules for rare mitochondrial diseases

With a $50M series A led by NEA, Reneo hopes to generate Phase I data for its rare mitochondrial diseases therapy

With a $50 million series A led by NEA and a management team guided by veterans of Shire takeout Lumena, Reneo believes its small molecule could carve out a niche in the rare genetic mitochondrial diseases space.

Reneo Pharmaceuticals Inc. is developing PPARδ agonist REN001, which it licensed from vTv Therapeutics Inc., in separate Phase I trials to treat fatty acid oxidation disorders (FAOD) and primary mitochondrial myopathy (PMM). Data from the trials are expected in 1Q20, according to Reneo co-founder, President and CEO Niall O’Donnell.

O’Donnell told BioCentury that vitamin or dietary supplements have anecdotally provided FAOD and PMM patients with modest benefits to help address their symptoms, including problems with fat breakdown, low blood sugar and dysfunctional ATP production. However, there are no clinical data to support the effectiveness of these approaches, according to O’Donnell, and there are no approved therapies for the indications.

Reneo said Monday it raised the series A to help advance REN001. In addition to New Enterprise Associates, other investors in the round include Lundbeckfonden Ventures, Pappas Capital and RiverVest Venture Partners, of which O’Donnell is managing director.

vTv has said PPARδ agonists can increase mitochondrial biogenesis gene expression in mice as well as decrease blood glucose, improve insulin sensitivity and regulate inflammation. In initial Phase I studies and in animal models, REN001 decreased LDL cholesterol and triglycerides while increasing HDL cholesterol.

O’Donnell identified two other companies with late-stage therapies for FAOD and PMM: Ultragenyx Pharmaceutical Inc. and Stealth BioTherapeutics Corp.

Ultragenyx plans to submit mid-year an NDA to FDA for triheptanoin (UX007) to treat long-chain FAOD. The product is a synthetic compound that provides medium-length, odd-chain fatty acids that are metabolized to replace intermediate substrates in fatty acid oxidation and in the tricarboxylic acid (TCA) cycle.

Stealth’s elamipretide, a mitochondrial-targeting tetrapeptide that binds and stabilizes cardiolipin to promote electron transfer and prevent apoptosis, is in Phase III testing for PMM. Top-line data are expected by year end.

Other disease-modifying approaches for mitochondrial diseases include gene editing to eliminate mutant mitochondrial genes and gene therapies to replace the damaged mitochondrial DNA.

While O’Donnell and NEA’s Ed Mathers said it was difficult to compare REN001 with these other methods, Mathers believes there is space in the field for Reneo’s small molecule disease-modifying approach. O’Donnell added that once initial therapies for FAOD and PMM get approved, regulatory agencies could be more open to backing alternative treatment options.

O’Donnell was interim CMO of rare liver disease and metabolic disorders company Lumena Pharmaceuticals Inc., which Shire plc acquired for $260 million up front in 2014. NEA was an investor in Lumena, where Mathers held a board seat (see “Luminous ROI”).

Reneo’s executive team also includes Wendy Johnson as COO, Alejandro Dorenbaum as CMO and Lynn Purkins as VP of clinical operations. Johnson was interim COO of AmpliPhi Biosciences Corp. and remains a board member; Dorenbaum was CMO of Lumena and Allakos Inc.; and Purkins was founder and chief development officer at Ziarco Group Ltd., which was acquired by Novartis AG in 2017.

In addition to O’Donnell and Mathers, Reneo’s board includes co-founder and executive chairman Mike Grey, who was Lumena’s president and CEO; Lundbeckfonden’s Johan Kördel; Pappas’ Arthur Pappas; and BioMarin Pharmaceutical Inc. CSO Lon Cardon.

O’Donnell said the series A financing will provide the company with runway through the end of next year and enable the company to complete the two Phase I studies and develop REN001 for up to two additional, undisclosed indications.


Reneo Pharmaceuticals Inc.

San Diego, Calif.

Technology: PPARδ agonist for rare mitochondrial diseases

Disease focus: Endocrine/Metabolic

Clinical status: Phase I

Founded: 2014 by Niall O’Donnell, Mike Grey, Susan Dubé

University collaborators: None

Corporate partners: vTv Therapeutics Inc.

Number of employees: 9

Funds raised: $50 million

Investors: New Enterprise Associates, Lundbeckfonden Ventures, Pappas Capital and RiverVest Venture Partners

CEO: Niall O’Donnell

Patents: Undisclosed

Companies and Institutions Mentioned

Allakos Inc. (NASDAQ:ALLK), San Carlos, Calif.

AmpliPhi Biosciences Corp. (NYSE-A:APHB), San Diego, Calif.

BioMarin Pharmaceutical Inc. (NASDAQ:BMRN), San Rafael, Calif.

Novartis AG (NYSE:NVS; SIX:NOVN), Basel, Switzerland

Reneo Pharmaceuticals Inc., San Diego, Calif.

Stealth BioTherapeutics Corp. (NASDAQ:MITO), Newton, Mass.

Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), Novato, Calif.

vTv Therapeutics Inc. (NASDAQ:VTVT), High Point, N.C.


PPARδ - Peroxisome proliferation activated receptor δ

How to gain access

Continue reading with a
two-week free trial.