CTHRC1

Phenomic and Shape are adding additional fuel to the warming hype around AI and machine learning's impact on drug development. Phenomic AI has largely lived off the grid since launching more than three years ago, but it’s now sprinting onto the scene with a second collaboration in as many days, this time with Astellas.  Twenty-four hours after announcing a target identification deal with Boehringer Ingelheim worth more than $500 million, Phenomic is back. The terms of the deal with Astellas-owned cell therapy biotech Xyphos Biosciences weren’t disclosed Thursday but Phenomic says the work will involve an antibody for the tumor stroma target identified by its scTx platform.  “I think you'll hear more from us very soon in terms of collaborations, in terms of the pipeline [and] the company more broadly,” CEO Girish Aakalu, Ph.D., said in an interview on Monday ahead of the Boehringer deal. Evidently “very soon” meant one day.  Aakalu said at the time that the company was also advancing an internal pipeline, with a lead asset aimed at a novel solid tumor target, CTHRC1. The full list of assets in the works has yet to be disclosed but Aakalu teed up 2024 as a year to watch. He was conscientious of not overloading his staff—some 20 people across Toronto and Massachusetts—with too much work too quickly.  “ScTx, our platform, delivers more ideas than we can really take advantage of,” he said. “And so we’ll ultimately need to be able to balance how much effort are we spending on partnership versus internal drug discovery.”  Phenomic was not the only AI biotech to tout new business development work Thursday. ShapeTX is expanding a collaboration with Roche after the Swiss pharma tacked on a new target to the partnership first announced in August 2021. The biotech hopes to use its RNA-editing platform to design “a potential one-time therapy for patients with high unmet needs for an undisclosed disease affecting millions of people worldwide.”  Financial details were kept under wraps but Shape will earn a milestone payment with the potential for additional biobucks. Shape will take on early preclinical development with Roche responsible for preclinical finishing touches, clinical development and commercialization.  The expanded deal with Roche comes less than three months after Shape inked an eye disease-focused deal with Otsuka worth $1.5 billion. The company raised a $112 million series B back in July 2021, which was slated to be spent in part on growing the RNA technology into “broad industry verticals.”

AI-based drug developer Phenomic is set for a busy 2024 with potentially more deals and disclosures about its internal pipeline. Phenomic AI has been keeping a low profile since launching in October 2020 with $6 million. But that’s set to change, with a new partnership jumpstarting what’s expected to be a busy 2024.  The Canadian company is teaming up with Boehringer Ingelheim on a target identification collaboration with more than $500 million at stake, including $9 million in upfront cash. In an interview with Fierce Biotech, Phenomic CEO Girish Aakalu, Ph.D., wouldn’t disclose how many targets the biotech is on the hook for, only confirming that “the terms are contingent on delivery as they always are.”  The targets will take on the tumor stroma, a complex structure made up of connective tissue that broadly helps tumors to stay intact. Cancer cells rely on stroma as both a defensive shield from the immune system's counterattack and a bridge to other parts of the body that can help feed the tumor. Phenomic and Boehringer both hypothesize that drugging sites in the stroma directly could spur a new class of cancer therapies.  Phenomic believes its single-cell RNA computing platform, dubbed scTx, will be the key that unlocks these targets. Aakalu said the platform not only provides a high-resolution glimpse at the stroma but uses significant statistical power to pull out valuable insights about the biology that can result in new therapeutic targets and, ultimately, drugs.  The biotech’s dataset now includes some 24 million cells, the CEO added. From there, targets are tested against a suite of in-house in vitro and in vivo assays. What Boehringer ultimately receives are targets that are validated and put into context, based on data produced by the platform.  Target identification pacts are just the tip of the iceberg, however, with more to come in the months ahead. Phenomic is advancing its own internal drug candidate aimed at CTHRC1, a relatively new gene first identified in 2005 that is associated with solid tumors. It means Phenomic is joining the growing ranks of AI and machine learning companies like Recursion, Exscientia and Benevolent AI, which are also drug developers.  “Our intent is to be a therapeutics company, but one with a platform that's powerful enough that we can help others as well,” Aakalu said. When asked about the mixed clinical track record of some AI companies to date, the CEO said the proof is always going to be in the experimentation of targets or molecules generated by machine learning.  “What I can say is that novel targets that we've identified have seemed to prove themselves out so far, which is exciting for us and hopefully for patients in the future,” he said.  The full pipeline is still under wraps, but more is set to be revealed in 2024. That includes more deals like the one announced Wednesday, Aakalu previewed. As for available cash, Aakalu said the company wasn’t fundraising yet but would be soon. 

SOUTH SAN FRANCISCO, Calif., Sept. 11, 2023 (GLOBE NEWSWIRE) -- Pliant Therapeutics, Inc. (Nasdaq: PLRX), a clinical stage biotechnology company focused on discovering and developing novel therapeutics for the treatment of fibrosis, today announced presentations made at the European Respiratory Society (ERS) International Congress 2023 taking place from September 9, 2023 to September 13, 2023. “We are pleased to be sharing non-clinical and clinical data at this important congress, including, for the first time at a scientific session, the final results from our INTEGRIS-IPF Phase 2a trial. Data from this trial support the late-stage development of bexotegrast as part of the BEACON-IPF trial and highlight our commitment to developing potential treatments for fibrotic diseases,” said Éric Lefebvre, M.D., Chief Medical Officer at Pliant Therapeutics. Safety, tolerability and antifibrotic activity of bexotegrast: Phase 2a INTEGRIS-IPF Study (NCT04396756) Findings from the 24-week analysis of our recently completed INTEGRIS-IPF Phase 2a trial of bexotegrast in patients with idiopathic pulmonary fibrosis (IPF) were presented in late-breaking oral and e-poster forms. Results showed that bexotegrast at 320 mg was well tolerated for up to 40 weeks of treatment with no discontinuations due to treatment-emergent adverse events occurring from Week 12 to Week 40. Additionally, over 24 weeks, a durable treatment effect on forced vital capacity (FVC) was observed in a population predominantly using IPF background therapies (nintedanib or pirfenidone). Quantitative lung fibrosis (QLF) imaging continued to demonstrate the antifibrotic mechanism of bexotegrast: at Week 24, the proportion of bexotegrast 320 mg-treated participants who experienced a stabilization or improvement of fibrosis was twice as high as those in the placebo group. Dual αVβ6/αVβ1 integrin inhibitor bexotegrast reduces fibrogenesis in pathological cell populations present in the fibrotic human lung Results from a single nuclei RNASeq analysis of bexotegrast-treated precision-cut lung slices prepared from fibrotic human tissue were presented in oral and poster forms. Results showed that bexotegrast treatment reduced the expression of pro-fibrogenic genes and pathways in pro-fibrotic (CTHRC1+) fibroblasts, as well as in aberrant basaloid cells known to express integrin αVβ6. Circulating ITGB6 levels are elevated in patients with IPF and reduced following lung transplant Results from a study comparing serum concentrations of integrin β6 in patients with IPF (pre/post-transplant) and healthy subjects was presented in poster form. Results showed that serum concentrations of integrin β6 were significantly elevated in patients with IPF compared to healthy controls, and that levels were significantly reduced in patients with IPF following lung transplant. Further analysis of circulating integrin β6 in clinical trials may help to better characterize its utility as an early biomarker of response to anti-fibrotic therapy. Posters presented at the 2023 ERS International Congress are also available on Pliant’s website under the Publications section at https://pliantrx.com/publications. About Pliant Therapeutics, Inc.Pliant Therapeutics is a clinical stage biopharmaceutical company focused on discovering and developing novel therapies for the treatment of fibrosis. Pliant's lead product candidate, bexotegrast (PLN-74809), is an oral, small molecule, dual selective inhibitor of αvß6 and αvß1 integrins that is in development in the lead indications for the treatment of idiopathic pulmonary fibrosis, or IPF, and primary sclerosing cholangitis, or PSC. Bexotegrast has received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) in IPF and PSC and Orphan Drug Designation from the European Medicines Agency in IPF and PSC. Pliant has initiated BEACON-IPF, a Phase 2b trial of bexotegrast in IPF. Pliant has also developed PLN-1474, a small molecule, selective inhibitor of αvß1 integrin for the treatment of nonalcoholic steatohepatitis, or NASH with liver fibrosis. Pliant has initiated a Phase 1 study for its third clinical program, PLN-101095, a small molecule, dual-selective inhibitor of αvß8 and αvß1 integrins, that is being developed for the treatment of solid tumors. In addition to clinical stage programs, Pliant currently has a preclinical program targeting muscular dystrophies. For additional information, please visit: www.PliantRx.com. Follow us on social media Twitter, LinkedIn, Facebook and YouTube. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those regarding the safety, tolerability, pharmacodynamics and therapeutic potential of bexotegrast; our plans for the future development of bexotegrast, PLN-101325 and PLN-101095; bexotegrast’s potential to become a treatment for IPF or PSC; the anticipated timing of data and progress from our clinical studies; discussions with regulatory authorities; the sufficiency of our cash runway to fund operations into the second half of 2026. Because such statements deal with future events and are based on our current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Pliant Therapeutics could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including those related to the development and commercialization of our product candidates, including any delays in our ongoing or planned preclinical or clinical trials, the impact of current macroeconomic and marketplace conditions, including lingering effects of the COVID-19 pandemic, on our business, operations, clinical supply and plans, our reliance on third parties for critical aspects of our development operations, the risks inherent in the drug development process, the risks regarding the accuracy of our estimates of expenses and timing of development, our capital requirements and the need for additional financing, including the availability of additional term loans under our loan facility, and our ability to obtain and maintain intellectual property protection for our product candidates. These and additional risks are discussed in the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in our Quarterly Report on Form 10-Q for the three months ended June 30, 2023 which is available on the SEC's website at www.sec.gov. Unless otherwise noted, Pliant is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. Investor and Media Contact:Christopher KeenanVice President, Investor Relations and Corporate CommunicationsPliant Therapeutics, Inc.ir@pliantrx.com