DUBLIN – For quite some time, cardiometabolic disease has been largely off the map for most small biotechs and for the venture capital investors that support them. Large, undifferentiated indications dominated by powerful incumbents did not generally offer much of a look in for smaller firms. Cancer and orphan indications, by their very nature, have offered a better bet, because of the bite-sized patient populations and the requirement for smaller scale clinical trials. Is that situation about to change? Maybe, maybe not was the mixed message arising from a Bio-Europe Spring 2020 virtual panel discussion on cardiometabolic disease.

For Amanda Chaperot, partner at Paris-based VC firm Seventure, niche indications in the cardiometabolic space can be a worthwhile investment in their own right – or also a stepping stone into something bigger. Alnylam Pharmaceuticals Inc. – hardly a niche operator anymore – and Dicerna Pharmaceuticals Inc. are both bringing their respective siRNA platforms to bear on primary hyperoxaluria, a genetic condition that affects the kidneys, which results in the overproduction of oxalate. It has probably been viewed by most through the rare disease rather than the cardiometabolic lens. “We can also see these as test cases for modalities, which can then expand into the other, broader indications,” Chaperot said. It also represents a good example of a novel modality entering a space that has long been viewed as weighing on the conservative in terms of adopting new drug modalities.

For Merck & Co. Inc., any licensing opportunity in the cardiometabolic space must have broad applicability, even if it starts off as a niche play. “I think that’s an absolute requirement, actually, for niche, orphan or smaller indications, that they have a line of sight towards development in larger therapeutic areas or indications, because the Merck organization is simply not fit for picking up orphans or anything like that,” said Michel de Baar, executive director, business development and licensing, at Kenilworth, N.J.-based Merck. “Of course, if one modality can treat various orphans and thereby has a good potential in terms of size of patient population for us that would be acceptable as well,” he said. “But we’re not in the business of orphan drugs, and there are other companies that are much better suited to that.”

Bagsvaerd, Denmark-based Novo Nordisk A/S takes a case-by-case approach to the question, said Tomas Landh, vice president, innovation sourcing. “We don’t have active programs right now on the smaller niche indications in diabetes [or] obesity,” he said. But the company is open to dialogue with firms that are operating in such areas. “We see this as a means for small biotechs to really take a small step into the arena of diabetes and obesity,” he said. “That’s why we try to help and shape those early programs.” Obesity offers more niche indications than diabetes. Prader-Willi, a genetic condition in which children develop an insatiable appetite, which leads to obesity and diabetes, is a good example and an area in which several biotechs are active. Diabetes is harder to carve up into smaller patient populations. “You can start to stratify type 2 diabetes as well for sure, but you end up with very large populations anyway,” Landh said.

For Merck, its focus is more on science than on specific conditions. “The whole organization in Merck is shifting towards more process and systems thinking instead of therapeutic area and indication thinking,” de Baar said. “As an example, if you look at NASH, which is a large indication, of course, there’s the metabolic aspect, the inflammatory aspect and there’s the fibrotic aspect.” Inflammation is hugely important in nonalcoholic steatohepatitis, or NASH, he added, but it is also in CNS disease and cardiac disease. So the present focus is more on pathways that may be relevant in several indications rather than on drugs geared solely at a single therapeutic area.

Jonas Renz, managing director and co-founder, Secarna

Meanwhile, the lead program at antisense oligonucleotide drug discovery firm Secarna Pharmaceuticals GmbH & Co. KG hit a key a milestone Monday, March 23. The Munich-based company signed a research, development and transfer agreement with its collaboration partner, Lipigon Pharmaceuticals AB, of Umeå, Sweden, under which Lipigon takes on responsibility for taking forward an antisense oligonucleotide development program targeting two genes implicated in dyslipidemia, angiopoietin-like protein 3 (ANGPTL3) and ANGPTL4. The former has been the focus of many drug campaigns. The latter less so. “I think that’s where the magic comes in,” Secarna’s managing director and co-founder, Jonas Renz, told BioWorld. “Nobody so far… has figured out a way to target both of them concurrently,” he said. “Lipigon is now bringing both of these ideas together in one therapeutic, and that’s quite novel.”

The program is about 18 months from entering clinical trials. The molecules involved are based on third-generation locked nucleic acid (LNA) technology, which is about 10-fold more potent than its predecessor, Renz said. “That’s opened up the window for antisense development.”

Secarna is a platform company rather than a cardiometabolic disease specialist. It has LNA across a broad range of areas, including fibrosis, immuno-oncology, immunology, CNS disease and antiviral drug discovery. In the latter sphere, it is in the process of adding a new program, which will target all coronaviruses. It will probably be too late to address the present pandemic, Renz said, but the company is finalizing a collaboration with a Chinese institute, in the expectation that there will be future coronavirus outbreaks, which may not be addressed by the current vaccine development efforts directed against SARS-CoV-2. “We’ve obviously going full-steam ahead with that one,” Renz said. “This would be an ideal therapeutic to stockpile for the next coronavirus outbreak.”