Pliant Pushes Forward With IPO Plans to Back Fibrosis Drug Studies

Xconomy San Francisco — 

Pliant Therapeutics has a pipeline of experimental fibrosis treatments and a research alliance with Novartis. Now the biotech is preparing an IPO to raise cash to advance its clinical-stage programs.

In paperwork filed with securities regulators, Pliant set an $86 million IPO target. That amount is a placeholder figure as the South San Francisco-based biotech determines how many shares to sell and at what price. If the company succeeds in going public, Novartis (NYSE: NVS) will boost its stake in its smaller partner. Concurrent with the stock sale, the Swiss pharmaceutical giant will purchase $10 million worth of Pliant shares at the IPO price, according to the filing.

Pliant’s therapeutic focus is fibrosis, a thickening and hardening of connective tissue that leads to scarring and organ damage. The condition can develop in the lungs, liver, kidneys, and elsewhere. The company’s first fibrosis target is idiopathic pulmonary fibrosis (IPF), which occurs in the lungs. IPF affects an estimated 140,000 patients in the US annually, each of them having life expectancy between three and five years from diagnosis, Pliant says in the filing. Those in late stages of the disease may require a lung transplant, though not all patients are eligible, Pliant says.

Two drugs developed specifically for IPF are currently on the market. Pirfenidone (Esbriet), sold by Roche unit Genentech, was approved by the FDA in 2017. Boehringer Ingelheim won the FDA nod in 2019 for nintedanib (Ofev) in 2014. While those those drugs slow the decline of lung function, Pliant says they don’t stop the progression of IPF and they come with the risk of dangerous side effects. Pliant is developing a fibrosis treatment that it says could be more effective and safer than currently available drugs.

Fibrosis differs depending on where in the body it occurs, but Pliant says the condition stems from dysregulation of tissue repair pathways. The company points specifically to a signaling pathway governed by a protein called transforming growth factor beta (TGF-beta). This protein is activated in response to tissue injury, contributing to collagen production and tissue healing, Pliant says in its filing. Fibrosis develops when that protein is continuously activated—even when there is no injury.

Pliant is developing drugs intended to treat fibrosis by blocking receptors for integrins, proteins that mediate the release of the TGF-beta. Speaking to Xconomy in March, Pliant CEO Bernard Coulie described integrins as a “master switch” for TGF-beta. Turning off that switch could stop the activation of the protein that drives the disease, he said. Integrin-blocking drugs have already reached the market for other diseases but these medicines come with side effects risks because integrin receptors are found throughout the body. Pliant says its drugs could offer a safer alternative by targeting two integrins found in high levels in fibrotic tissue but in low amounts in healthy tissue.

Pliant is currently enrolling IPF patients in two Phase 2a studies testing its lead program, PLN-74809. A separate mid-stage study evaluating the drug in primary biliary cholangitis (PBC), a form of fibrosis affecting the bile ducts, is expected to start in the second half of this year, according to the filing. Pliant adds in the filing that the drug has potential applications addressing other lung and liver disorders characterized by fibrosis, as well as end-stage-renal disease.

Other companies are in the chase for new fibrosis drugs. Galapagos (NASDAQ: GLPG), Biogen (NASDAQ: BIIB), AbbVie (NYSE: ABBV), and Gilead Sciences (NASDAQ: GILD) are among the companies developing medicines that address some aspect of the TGF-beta pathway, according to the IPO filing. But Pliant says it stands apart from them as the only company developing an oral, small molecule drug that selectively blocks integrins.

The partnership with Novartis is focused on a different drug. Last year, the pharmaceutical giant paid Pliant $80 million up front for global rights to PLN-1474, a potential treatment for fibrosis in patients with nonalcoholic steatohepatitis, a liver disorder. Pliant is currently enrolling patients in a Phase 1a study that will be paid for by Novartis. Despite delays caused by the COVID-19 pandemic, Pliant says in its filing that data from the study are expected by the end of this year.

Pliant’s IPO filing comes two months after the company closed a $100 million financing led by Novartis. According to the prospectus, the pharma giant’s stake in its partner is 6.2 percent. The Series C round of funding included so-called crossover investors, firms that invest in both private and public companies. Raising crossover cash is viewed as a sign that a company is preparing to go public.

To date, Pliant says it has raised more than $220 million from investors. The company’s largest shareholder is venture capital firm Third Rock Ventures, which owns 32.3 percent, according to the IPPO filing. Third Rock launched Pliant in 2016, backing the biotech with $45 million.

Pliant has applied for a Nasdaq listing under the stock symbol “PLRX.”

KIROMIC BIOPHARMA PREPS IPO

In other biotech IPO news, Kiromic Biopharma is preparing to go public to address what it says is one of the main challenges for cancer immunotherapies: identifying targets. The Houston-based company says in its filing that its technology, called Diamond, identifies new immunological targets for T cells and B cells. These targets can then be used to create antibody drugs, T cell therapies, T cell receptor therapies, chimeric antigen (CAR) T cell therapies, and vaccines, Kiromic says in its filing.

Diamond analyzes more than 1 billion data points from a digital library of clinical studies as well as genomic and proteomic datasets. Kiromic says its technology identifies and prioritizes lists of genes expressed in a particular disease, providing additional data on the status of those genes across the patient population. Another Kiromic technology, CancerSplice, addresses isoforms, which are variants of a target protein that can make it difficult for T cells to bind to a target and kill a cancer cell. The CancerSplice software predicts the correct isoform targets for T cells.

Kiromic set a preliminary $20 million IPO target to support its pipeline of four preclinical programs. The company says its lead product candidate, ALEXIS AIDT-1, is a CAR being developed to target AIDT-1, an antigen expressed on the surface of B cells, including malignant ones. The company says it expects this therapy will target B cell malignancies that are difficult to treat with currently available CAR therapies. Kiromic says this program is currently undergoing preparation for the tests needed to support an application to begin clinical testing, which is expected to start in the second half of this year.

Kiromic formed in 2012 with a strategy to apply artificial intelligence to the development of cancer immunotherapies. Maurizio Chiriva Internati, the company’s chairman and CEO since February 2018, owns a 34.7 percent stake in the firm, making him its largest shareholder, the filing shows. The company reported spending $1.2 million on research and development in 2019. It finished last year with $1.9 million in cash. Kiromic says it plans to apply for a listing on the NYSE American exchange under the stock symbol “KRBP.”

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