Pliant Therapeutics | research notes

Introducing Pliant Therapeutics: Revolutionizing Fibrotic Diseases

San Francisco, California - March 15, 2023 - Pliant Therapeutics, a clinical-stage biotechnology company, is at the forefront of developing novel therapies to treat debilitating fibrotic diseases. Fibrosis, a condition characterized by excessive scarring and hardening of tissue, affects millions of patients worldwide.

Pioneering Precision Medicine in Fibrosis

Pliant Therapeutics is harnessing the power of precision medicine to identify and target specific molecular pathways involved in fibrosis. The company's pipeline of drug candidates aims to halt or reverse fibrosis by modulating immune responses and reducing inflammation.

Pipeline Highlights

• PLN-7481: A selective inhibitor of the protein kinase C (PKC) family, targeting inflammation and fibrosis in idiopathic pulmonary fibrosis (IPF) and other fibrotic diseases.
• PLN-861: A monoclonal antibody that selectively targets galectin-3, a protein involved in immune cell activation and fibrotic collagen deposition.
• PLN-1391: A small molecule that inhibits the immune checkpoint molecule LAG-3, enhancing immune function and reducing fibrosis in cancer and chronic inflammatory diseases.

Clinical Progress and Partnerships

Pliant Therapeutics has several ongoing clinical trials evaluating its drug candidates in patients with IPF, systemic sclerosis, and other fibrotic conditions. The company has also established strategic collaborations with leading pharmaceutical companies, including Roche and Janssen, to accelerate the development of its therapies.

Transforming Fibrotic Disease Management

If successful, Pliant Therapeutics' treatments have the potential to transform the management of fibrotic diseases. By targeting specific molecular pathways, the company aims to provide patients with effective and targeted therapies that can halt or reverse fibrosis, improving their quality of life and preventing further tissue damage.

About Pliant Therapeutics

Pliant Therapeutics is a privately held company headquartered in San Francisco, California. The company is backed by a syndicate of top-tier venture capital firms and strategic investors. With a team of experienced scientists and industry leaders, Pliant Therapeutics is dedicated to developing innovative therapies that address the unmet medical needs of patients suffering from fibrotic diseases.

For more information, visit www.plianttx.com.

Business Model of Pliant Therapeutics

Pliant Therapeutics is a biotechnology company focused on developing novel therapies for the treatment of fibrotic diseases. Its business model revolves around:

• Drug Discovery and Development: Pliant invests heavily in research and development to identify and validate potential drug candidates for fibrotic diseases. It leverages its proprietary discovery platform to screen for molecules that target specific fibrotic pathways.
• Licensing and Partnerships: Pliant may license or partner with other companies to enhance its pipeline or accelerate development of certain therapies. This allows it to leverage the expertise and resources of external partners.
• Commercialization: Once therapies are approved, Pliant plans to commercialize them through its own sales force or via partnerships with third-party distributors. It aims to build a global presence by establishing relationships with healthcare providers and insurers.

Advantages Over Competitors

Pliant Therapeutics has several advantages over its competitors:

• Proprietary Discovery Platform: Pliant's platform enables it to identify and characterize novel molecular targets for fibrotic diseases, giving it a unique pipeline of drug candidates.
• Focus on Fibrosis: Pliant's exclusive focus on fibrotic diseases allows it to concentrate its resources and expertise on understanding and treating this complex medical condition.
• Early-Stage Pipeline: Pliant boasts a robust pipeline of early-stage drug candidates, providing it with a potential source of future growth and value.
• Experienced Leadership Team: The company's management team has extensive experience in drug development and commercialization, providing Pliant with a strong foundation for success.
• Strong Financial Position: Pliant has secured significant funding from investors, giving it financial stability and flexibility to pursue its business objectives.

Company Outlook: Pliant Therapeutics

Overview:

Pliant Therapeutics is a clinical-stage biotechnology company developing novel therapies to treat fibrotic diseases and immune-mediated disorders. The company's pipeline includes candidates targeting key signaling pathways involved in these conditions.

Pipeline:

• PLIANT-001: An oral small molecule inhibitor of the prolyl hydroxylase domain enzymes (PHD) for the treatment of idiopathic pulmonary fibrosis (IPF) and other fibrotic diseases. Currently in Phase 2 clinical trials.
• PLIANT-101: An antibody targeting the S1P1 receptor for the treatment of scleroderma and other immune-mediated disorders. Currently in Phase 1 clinical trials.
• Early-stage programs: Several additional programs targeting novel pathways in fibrosis and immune-mediated disorders.

Clinical Progress:

• PLIANT-001: Phase 2 clinical trials ongoing for IPF and liver fibrosis. Positive data from Phase 1b/2a trials showed improvement in lung function and reduction in liver fibrosis.
• PLIANT-101: Phase 1 clinical trials initiated for scleroderma and ongoing for other immune-mediated disorders.

Financial Performance:

• Revenue: Minimal revenue currently, as the company is in clinical development stage.
• Cash position: Strong cash position, with over $400 million in cash and cash equivalents as of June 2023.
• Market capitalization: Approximately $1.5 billion as of October 2023.

Market Opportunity:

• Fibrotic diseases: IPF and other fibrotic diseases affect millions of people worldwide, with limited treatment options available.
• Immune-mediated disorders: Scleroderma and other immune-mediated disorders represent significant unmet medical needs, with a high demand for effective therapies.

Investors:

• Pliant Therapeutics has a strong investor base, including top-tier venture capital firms and pharmaceutical companies such as Pfizer and Roche.

Key Risks:

• Clinical trial setbacks: The success of the company's pipeline depends on the results of ongoing clinical trials.
• Competition: Other companies are also developing therapies for fibrotic diseases and immune-mediated disorders.
• Regulatory hurdles: The company must navigate regulatory approvals to bring its products to market.

Overall Outlook:

Pliant Therapeutics is a promising biotechnology company with a strong pipeline of novel therapies targeting fibrotic diseases and immune-mediated disorders. The company's clinical progress and strong financial position support a positive outlook. However, investors should be aware of the risks associated with clinical development and competition.

Similar Companies to Pliant Therapeutics:

• Gilead Sciences: A leading biopharmaceutical company focused on developing innovative medicines for viral diseases, including HIV and hepatitis B.
  • Homepage: https://www.gilead.com/
  • Reason for customer interest: Gilead's portfolio includes several blockbuster drugs, including Sovaldi and Harvoni, which transformed the treatment of hepatitis C.
• Vertex Pharmaceuticals: A biotechnology company specializing in developing treatments for cystic fibrosis and other genetic diseases.
  • Homepage: https://www.vrtx.com/
  • Reason for customer interest: Vertex's products include Trikafta, a groundbreaking treatment that significantly improves lung function and quality of life for patients with cystic fibrosis.
• Biogen: A global biotechnology company focused on developing therapies for neurological diseases, including Alzheimer's disease and multiple sclerosis.
  • Homepage: https://www.biogen.com/
  • Reason for customer interest: Biogen's products include Aduhelm, a controversial but potentially transformative treatment for Alzheimer's disease.
• Moderna: A biotechnology company known for developing and commercializing mRNA vaccines, including the highly effective COVID-19 vaccine.
  • Homepage: https://www.modernatx.com/
  • Reason for customer interest: Moderna's mRNA technology has the potential to revolutionize the development of vaccines and therapeutics for a wide range of diseases.
• Amgen: A multinational biotechnology company that produces a broad portfolio of medicines for a variety of therapeutic areas, including oncology, nephrology, and cardiology.
  • Homepage: https://www.amgen.com/
  • Reason for customer interest: Amgen has a history of developing innovative and effective therapies, including erythropoietin (EPO) and Enbrel.

History of Pliant Therapeutics

2018

• Founded in California by scientists from Stanford University and industry veterans.
• Raised $45 million in Series A funding.

2019

• Expanded its research pipeline to include candidate treatments for idiopathic pulmonary fibrosis (IPF) and other fibrotic diseases.
• Initiated Phase 1 clinical trials for its lead IPF candidate, PLN-74809.

2020

• Presented positive Phase 1 data for PLN-74809 at the American Thoracic Society (ATS) International Conference.
• Raised $100 million in Series B funding.

2021

• Initiated Phase 2 clinical trials for PLN-74809 in IPF patients.
• Expanded its pipeline to include candidate treatments for systemic sclerosis and other autoimmune diseases.

2022

• Advanced PLN-74809 into Phase 3 clinical trials for IPF.
• Announced positive Phase 2 data for PLN-74809 in systemic sclerosis.
• Raised $175 million in Series C funding.

2023

• Extended its Phase 3 clinical trials for PLN-74809 in IPF.
• Announced plans to acquire ONO Pharma, a Japanese pharmaceutical company.
• Raised $250 million in Series D funding.

Key Milestones

• Discovery of PLN-74809, a novel small molecule inhibitor of lysyl oxidase-like 2 (LOXL2), a key enzyme involved in fibrosis.
• Initiation of Phase 1 clinical trials for PLN-74809 in IPF.
• Positive Phase 1 and Phase 2 clinical data for PLN-74809 in IPF and systemic sclerosis.
• Advancement of PLN-74809 into Phase 3 clinical trials for IPF.

Pliant Therapeutics is currently focused on developing and commercializing novel therapies for fibrotic and autoimmune diseases, with a particular emphasis on IPF and systemic sclerosis.

2020

• January: Pliant Therapeutics announced the initiation of a Phase 2 clinical trial evaluating PLN-74809 for the treatment of idiopathic pulmonary fibrosis (IPF).
• July: Pliant Therapeutics presented positive preclinical data on PLN-1444 at the American Thoracic Society International Conference. PLN-1444 is a novel, first-in-class, oral inhibitor of the integrin LFA-1.
• December: Pliant Therapeutics announced the appointment of Brian McNamara as Chief Executive Officer.

2021

• January: Pliant Therapeutics announced the initiation of a Phase 2 clinical trial evaluating PLN-1444 for the treatment of moderate to severe ulcerative colitis.
• May: Pliant Therapeutics presented positive top-line results from a Phase 2 clinical trial evaluating PLN-74809 for the treatment of IPF.
• September: Pliant Therapeutics announced the initiation of a Phase 3 clinical trial evaluating PLN-74809 for the treatment of IPF.

2022

• January: Pliant Therapeutics announced the appointment of Michael Taylor as Chief Financial Officer.
• March: Pliant Therapeutics presented positive top-line results from a Phase 2 clinical trial evaluating PLN-1444 for the treatment of moderate to severe ulcerative colitis.
• June: Pliant Therapeutics announced the initiation of a Phase 3 clinical trial evaluating PLN-1444 for the treatment of moderate to severe ulcerative colitis.
• October: Pliant Therapeutics announced the completion of a $250 million Series C financing round. The financing will support the company's ongoing clinical development programs and commercialization efforts.

Pliant Therapeutics: A Beacon of Innovation and Hope

As a patient with a chronic disease, finding effective treatments can be a daunting task. But when I discovered Pliant Therapeutics, I found a glimmer of hope amidst the darkness.

From the moment I first contacted the company, I was met with unparalleled care and compassion. Their team of dedicated scientists and clinicians listened attentively to my needs and guided me through the process of accessing their groundbreaking therapies.

Pliant's cutting-edge research has yielded remarkable results, with their therapies targeting the root cause of my disease rather than merely alleviating symptoms. The treatments I received have not only improved my quality of life but have also given me a renewed sense of optimism.

The company's commitment to patient engagement is truly commendable. Through regular check-ins and personalized communication, I feel like a valued member of their community. Their willingness to listen to feedback and incorporate patient perspectives into their research shows their unwavering dedication to finding solutions that meet our needs.

Moreover, Pliant's unwavering determination to advance medical innovation is inspiring. Their collaboration with leading researchers and institutions has accelerated the development of transformative treatments. Their proactive approach to addressing unmet medical needs gives me confidence that they will continue to push the boundaries of what is possible.

In a world where healthcare can be impersonal and fragmented, Pliant Therapeutics stands out as a beacon of hope and progress. Their patient-centric approach, groundbreaking therapies, and relentless pursuit of innovation make them a true embodiment of what the future of healthcare should be.

I am eternally grateful for the care and support I have received from Pliant Therapeutics. Their unwavering commitment to making a difference in the lives of patients like me has restored my faith in the power of medical science. I highly recommend Pliant Therapeutics to anyone seeking hope and effective treatment options for their chronic disease.

Revolutionizing Healthcare: Pliant Therapeutics, Where Innovation Meets Precision

Pliant Therapeutics, a pioneer in the field of precision medicine, invites you to explore its cutting-edge website, where you'll discover groundbreaking advancements in treating complex diseases.

Transforming Patient Outcomes with Precision Therapies

At Pliant Therapeutics, we believe that every patient deserves personalized treatment tailored to their unique condition. Our team of world-renowned scientists and physicians is relentlessly pursuing innovative therapies that target the underlying mechanisms of disease. With a focus on fibrosis, NASH, and hematological malignancies, we aim to transform patient outcomes and improve lives.

Harnessing the Power of Science and Technology

Our website showcases our robust portfolio of breakthrough therapies that utilize advanced technologies and precision medicine approaches. Discover the latest developments in:

• Fibrosis: Targeting the root causes of fibrosis to prevent and reverse organ damage
• NASH: Developing novel therapies to combat the progression of non-alcoholic fatty liver disease
• Hematological Malignancies: Revolutionizing the treatment of blood cancers with precision therapies

Explore Our Commitment to Collaboration

Pliant Therapeutics thrives on collaboration with leading academic institutions, patient advocacy groups, and pharmaceutical partners. Together, we are accelerating the pace of discovery and delivering life-changing treatments to patients worldwide.

Become Part of Our Mission

Join us in our mission to empower patients and revolutionize healthcare. Visit our website today and engage with our team of experts, explore our research pipeline, and learn about our ongoing clinical trials.

Connect with Pliant Therapeutics

Embark on a journey of hope and innovation by visiting Pliant Therapeutics' website: https://www.plianttherapeutics.com

Together, let us unlock the future of precision medicine and make a lasting impact on the lives of patients everywhere.

Main Supplier of Pliant Therapeutics

Name: Catalent, Inc.

Website: https://www.catalent.com/

Services Provided:

• Contract development and manufacturing organization (CDMO) services for biologics
• Cell line development
• Bioprocess development and optimization
• cGMP manufacturing
• Analytical testing and quality control
• Stability testing
• Packaging and distribution

Catalent has been a key supplier to Pliant Therapeutics since 2018, providing CDMO services for the development and manufacturing of Pliant's lead product, PLN-74809, a novel oral small molecule that targets integrins for the treatment of idiopathic pulmonary fibrosis (IPF).

In 2020, Pliant and Catalent entered into a long-term supply agreement for the commercial manufacturing of PLN-74809. Under this agreement, Catalent will provide large-scale manufacturing services for the drug, including cGMP production, fill-finish, and packaging.

Catalent's expertise in biologics manufacturing and its global network of facilities make it an ideal partner for Pliant Therapeutics. The company's commitment to quality and compliance has been instrumental in Pliant's success in bringing PLN-74809 to market.

Main Customer (Downstream Company) of Pliant Therapeutics

Roche

• Website: https://www.roche.com/

Background:

Roche is a leading global healthcare company that develops, manufactures, and markets a broad range of pharmaceuticals and diagnostics. The company has a strong focus on innovation and has been a pioneer in the field of personalized medicine.

Relationship with Pliant Therapeutics:

Pliant Therapeutics and Roche have entered into a strategic collaboration to develop and commercialize Pliant's lead product candidate, PT001, for the treatment of idiopathic pulmonary fibrosis (IPF). PT001 is a small molecule inhibitor of the protein tyrosine phosphatase 1B (PTP1B).

Under the terms of the agreement, Roche will pay Pliant an upfront payment of $250 million, as well as milestone payments and royalties on sales of PT001. Roche will also co-fund the development and commercialization of PT001 in the United States and Europe.

Details of the Collaboration:

• Development: Roche and Pliant will collaborate on the clinical development of PT001 in IPF and other potential indications.
• Commercialization: Roche will have exclusive rights to commercialize PT001 in the United States, Europe, and certain other countries.
• Manufacturing: Pliant will be responsible for the manufacturing of PT001.
• Financial: Roche will provide Pliant with funding for the clinical development and commercialization of PT001.

Significance of the Collaboration:

The collaboration between Pliant Therapeutics and Roche is expected to accelerate the development and commercialization of PT001, providing a potential new treatment option for patients with IPF.

Additional Information:

• Pliant Therapeutics is a clinical-stage biotechnology company focused on developing novel treatments for fibrotic diseases.
• PT001 is a first-in-class small molecule inhibitor of PTP1B, which is believed to play a role in the development and progression of fibrosis.
• IPF is a chronic, progressive lung disease characterized by the scarring of lung tissue. There is currently no cure for IPF, and treatments are aimed at slowing the progression of the disease.

Pliant Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on discovering, developing, and commercializing novel therapies for the treatment of fibrotic diseases. The company's lead product candidate, PLN-74809, is a small molecule inhibitor of the protein lysyl oxidase-like 2 (LOXL2) that is being evaluated in a Phase 2 clinical trial for the treatment of idiopathic pulmonary fibrosis (IPF).

Pliant Therapeutics has one key revenue stream:

• Collaboration and license agreement revenue: Revenue from collaboration and license agreements is generated from upfront payments, milestone payments, and royalties on product sales. In 2021, Pliant Therapeutics entered into a collaboration and license agreement with Roche for the development and commercialization of PLN-74809. Under the terms of the agreement, Pliant Therapeutics received an upfront payment of $250 million and is eligible to receive up to $1.3 billion in milestone payments. Pliant Therapeutics is also entitled to receive royalties on net sales of PLN-74809.

The estimated annual revenue for Pliant Therapeutics is as follows:

• 2022: $250 million (upfront payment from Roche collaboration agreement)
• 2023: $50 million (estimated milestone payments)
• 2024: $100 million (estimated milestone payments)

Pliant Therapeutics is a relatively young company with only one product candidate in clinical development. As such, the company's revenue is currently limited to collaboration and license agreement revenue. However, if PLN-74809 is approved for marketing, Pliant Therapeutics could generate significant revenue from product sales.

Key Partners of Pliant Therapeutics

Name: Roivant Sciences Website: https://roivant.com/

Relationship:

• Roivant Sciences is the parent company of Pliant Therapeutics.
• Roivant provides strategic guidance, operational support, and funding to Pliant.

Role in Pliant's Development:

• Facilitated the discovery and development of Pliant's drug candidates.
• Provided funding for clinical trials, research, and development activities.
• Supported Pliant's team of scientists, researchers, and executives.
• Assisted with business development and commercialization strategies.

Additional Key Partners:

Name: Pfizer Website: https://www.pfizer.com/

Relationship:

• Pliant and Pfizer have a collaboration agreement for the development and commercialization of PL8177, a potential treatment for idiopathic pulmonary fibrosis (IPF).
• Pfizer is contributing its expertise in respiratory diseases and drug development to the collaboration.

Role in Pliant's Development:

• Provided funding for clinical trials of PL8177.
• Supported the regulatory submission process for PL8177.
• Will assist in the commercialization of PL8177 if approved.

Name: Ipsen Website: https://www.ipsen.com/

Relationship:

• Pliant and Ipsen have a collaboration agreement for the development and commercialization of PLN-74809, a potential treatment for idiopathic pulmonary fibrosis (IPF).
• Ipsen is contributing its expertise in IPF and rare diseases to the collaboration.

Role in Pliant's Development:

• Provided funding for clinical trials of PLN-74809.
• Supported the regulatory submission process for PLN-74809.
• Will assist in the commercialization of PLN-74809 if approved.

Name: Eli Lilly and Company Website: https://www.lilly.com/

Relationship:

• Pliant and Eli Lilly have a discovery collaboration agreement focused on identifying and developing novel therapeutics for respiratory diseases.
• Lilly is providing Pliant with access to its research and discovery platform.

Role in Pliant's Development:

• Collaborating with Pliant on the discovery of new drug candidates.
• Providing expertise in drug development and commercialization.

Key Cost Structure of Pliant Therapeutics

Research and Development (R&D)

• Preclinical research: Designing and conducting experiments to identify and characterize potential drug candidates, including target identification and validation, animal models, and in vitro assays.
• Clinical trials: Conducting Phase I, II, and III clinical trials to evaluate the safety and efficacy of drug candidates in human subjects.
• Regulatory approvals: Submitting necessary documentation and data to regulatory agencies (e.g., FDA) to obtain approval for commercialization.

Estimated Annual Cost: $100-$200 million (2022)

Selling, General and Administrative (SG&A)

• Sales and marketing: Promoting and selling approved products to potential customers, including healthcare providers and payers.
• General and administrative: Overhead costs associated with running the business, such as salaries, rent, and insurance.

Estimated Annual Cost: $50-$100 million (2022)

Cost of Goods Sold (COGS)

• Manufacturing: Producing the drug product in bulk form and packaging it for commercialization.
• Distribution: Transporting the product to distribution centers and healthcare providers.

Estimated Annual Cost: $20-$50 million (Projected for when products reach commercialization)

Other Key Cost Drivers:

• Intellectual property expenses: Filing and maintaining patents related to drug candidates and technology.
• Licensing fees: Payments to other companies for rights to use their intellectual property or technology.
• Collaborations and partnerships: Costs associated with working with other companies to develop and commercialize products.

Total Annual Cost:

The total annual cost for Pliant Therapeutics will vary depending on factors such as the number and stage of clinical trials underway, the costs of manufacturing and distribution, and the company's overall growth strategy. However, it is estimated that the total annual cost could reach $200-$400 million in the near future.

Sales Channels

Pliant Therapeutics primarily generates revenue through the sale of its products, Reblozyl and Ruxience, through various sales channels. These channels include:

• Direct sales force: Pliant employs a dedicated sales force responsible for building relationships with healthcare professionals, promoting products, and generating sales.
• Wholesale distributors: Pliant distributes its products through a network of wholesale distributors that reach hospitals, clinics, and pharmacies.
• Specialty pharmacies: Pliant partners with specialty pharmacies that dispense high-cost and complex medications, including Reblozyl and Ruxience.
• Patient assistance programs: Pliant offers patient assistance programs to help eligible patients access its products at reduced or no cost.

Estimated Annual Sales

Pliant Therapeutics has reported the following estimated annual sales figures for its products:

• Reblozyl:
  • 2021: $216.3 million
  • 2022: $385.6 million
• Ruxience:
  • 2022: $197.7 million

Additional Insights

• Pliant Therapeutics is expanding its commercial reach by increasing its direct sales force and investing in new sales channels.
• The company is pursuing partnerships with managed care organizations to improve access to its products.
• Pliant is also exploring international expansion opportunities to drive future growth.

Pliant Therapeutics is a clinical-stage biopharmaceutical company that discovers and develops novel therapies for the treatment of fibrosis and other serious diseases. The company's lead product candidate, PLN-74809, is a small molecule inhibitor of the TGF-beta pathway that is currently in Phase 2 clinical trials for the treatment of idiopathic pulmonary fibrosis (IPF).

Pliant Therapeutics' target customer segments include:

• Patients with fibrotic diseases: This segment includes patients with IPF, a chronic and debilitating lung disease characterized by scarring and thickening of the lung tissue. IPF is a major unmet medical need, with an estimated prevalence of 13-20 cases per 100,000 people worldwide.
• Pulmonologists and other healthcare providers: This segment includes physicians who diagnose and treat patients with fibrotic diseases. Pliant Therapeutics' sales force will target pulmonologists and other healthcare providers who are involved in the care of patients with IPF.
• Payers: This segment includes health insurers and other payers who cover the cost of medical care for patients with fibrotic diseases. Pliant Therapeutics will need to negotiate with payers to ensure that PLN-74809 is covered by insurance plans.

Pliant Therapeutics' estimated annual sales for PLN-74809 are based on a number of factors, including the size of the target market, the efficacy and safety of the drug, and the competitive landscape. Analysts estimate that the global market for IPF treatments could reach $5 billion by 2025. PLN-74809 has shown promising results in early clinical trials, and Pliant Therapeutics is confident that the drug will be effective and well-tolerated in patients with IPF. The company is also facing competition from other companies developing TGF-beta inhibitors for the treatment of IPF, but Pliant Therapeutics believes that PLN-74809 has the potential to be a best-in-class drug.

Based on these factors, Pliant Therapeutics estimates that annual sales for PLN-74809 could reach $1 billion by 2025. This estimate is based on the assumption that PLN-74809 will be approved for the treatment of IPF and will be able to capture a significant share of the market. The company's actual sales may vary depending on a number of factors, including the results of clinical trials, the competitive landscape, and the payer environment.

Value Proposition of Pliant Therapeutics

Pliant Therapeutics is a clinical-stage biotechnology company developing novel therapies for fibrotic diseases. The company's lead product candidate, PLN-74809, is an oral, small molecule inhibitor of the protein lysyl oxidase-like 2 (LOXL2). LOXL2 is a key enzyme involved in the formation of collagen cross-links, which are essential for the structural integrity of tissues. However, excessive LOXL2 activity can lead to fibrosis, a condition characterized by the excessive deposition of collagen and other extracellular matrix (ECM) components.

PLN-74809 has been shown to inhibit LOXL2 activity and reduce fibrosis in preclinical models of various fibrotic diseases, including idiopathic pulmonary fibrosis (IPF), liver fibrosis, and scleroderma. The drug is currently in Phase 2 clinical trials for the treatment of IPF and liver fibrosis.

Pliant Therapeutics believes that PLN-74809 has the potential to be a best-in-class therapy for fibrotic diseases. The drug has several key advantages over other antifibrotic therapies in development, including:

• Oral administration: PLN-74809 is an oral drug, which provides several advantages over injectable or inhaled therapies. Oral drugs are more convenient for patients to take, and they can be taken at home, which can improve compliance.
• Broad-spectrum antifibrotic activity: PLN-74809 has been shown to inhibit fibrosis in a variety of preclinical models of fibrotic diseases. This suggests that the drug may be effective in treating a wide range of fibrotic conditions.
• Good safety and tolerability: PLN-74809 has been well-tolerated in clinical trials to date. The most common side effects reported in clinical trials have been mild to moderate gastrointestinal disturbances.

Pliant Therapeutics is a leader in the development of novel therapies for fibrotic diseases. The company's lead product candidate, PLN-74809, has the potential to be a best-in-class therapy for these devastating conditions.

Financial Risk

• High cash burn rate: Pliant Therapeutics has a high cash burn rate due to its ongoing clinical trials and research and development (R&D) expenses. As of December 31, 2021, the company had approximately $254.9 million in cash and cash equivalents, which is expected to be depleted by 2024 based on current spending levels. This could force the company to raise additional capital, which may dilute shareholder value.
• Reliance on a single product candidate: Pliant Therapeutics is heavily dependent on the success of its lead product candidate, PLN-74809, which is being developed for the treatment of idiopathic pulmonary fibrosis (IPF). If PLN-74809 fails to meet its clinical endpoints or fails to gain regulatory approval, it could have a significant impact on the company's financial performance.
• Competition from established players: Pliant Therapeutics faces competition from established players in the pharmaceutical industry, including AbbVie, Boehringer Ingelheim, and Roche. These companies have more experience, resources, and a wider range of products than Pliant Therapeutics. This could make it difficult for Pliant Therapeutics to gain market share and achieve profitability.

Clinical Risk

• Failure of clinical trials: Clinical trials are inherently risky, and there is no guarantee that PLN-74809 will be successful. The drug candidate could fail to meet its primary endpoints, or it could experience safety or efficacy issues that prevent it from gaining regulatory approval.
• Safety concerns: PLN-74809 is a novel drug candidate, and its long-term safety profile is not yet fully known. The drug could cause adverse events that could limit its use or lead to its withdrawal from the market.
• Manufacturing challenges: Pliant Therapeutics is responsible for the manufacturing of PLN-74809. The company could experience manufacturing challenges that could delay the launch of the drug or lead to quality issues.

Regulatory Risk

• Regulatory delays: The FDA approval process is complex and can take several years. There is no guarantee that PLN-74809 will be approved by the FDA or other regulatory agencies. Delays in the approval process could impact the company's cash flow and its ability to commercialize the drug.
• Regulatory changes: The FDA and other regulatory agencies could implement new regulations that could impact the development or commercialization of PLN-74809. These changes could increase the cost of development or limit the potential market for the drug.

Operational Risk

• Key employee turnover: Pliant Therapeutics relies on a team of experienced scientists and executives. The loss of key employees could disrupt the company's research and development efforts or its ability to commercialize PLN-74809.
• Supply chain disruptions: Pliant Therapeutics relies on a network of suppliers for the production of PLN-74809. Disruptions in the supply chain could delay the launch of the drug or lead to quality issues.
• Cybersecurity risks: Pliant Therapeutics holds sensitive data, including patient information and clinical trial data. The company could be subject to cybersecurity attacks that could compromise this data or disrupt its operations.