Idiopathic Interstitial Pneumonias

Aerosolized 4D-710 was generally well tolerated with no inflammation in any lung biopsy across Cohorts 1 and 2 (1E15 & 2E15 vg; n=7) with up to 17 months follow-up Promising, reproducible, CFTR expression significantly above normal levels across all participants and all lung tissue samples collected (n=34), substantially exceeding target pro > Durable clinical activity demonstrated by improvements in quality of life by CFQ-R-RD and pulmonary function by ppFEV1 through 12 months in Cohort 1 FDA feedback on 4D-710 development path as monotherapy and in combination with approved CF modulator therapies expected in Q1 2024 Company to host webcast today, Wednesday, November 1, 2023 at 4:30 p.m. ET EMERYVILLE, Calif., Nov. 01, 2023 (GLOBE NEWSWIRE) -- 4D Molecular Therapeutics (Nasdaq: FDMT, 4DMT, or the Company), a genetic medicines company with three novel, highly targeted next generation AAV vectors currently in human clinical studies, today announced interim data from the Phase 1/2 AEROW clinical trial evaluating aerosolized 4D-710 for treatment of cystic fibrosis lung disease. Results will also be presented at the 2023 North American Cystic Fibrosis Conference (NACFC) in both plenary and symposium sessions on November 2-3. “We are pleased with the safety and tolerability of 4D-710 in participants in the AEROW study to date. Participants with cystic fibrosis in this clinical trial do not have the option of treatment with currently available disease modifying therapies and therefore have high unmet need,” said Jennifer L. Taylor-Cousar, M.D., MSCS, Professor, Departments of Medicine and Pediatrics, and Co-Director, Adult Cystic Fibrosis Program, Director, Cystic Fibrosis Foundation Therapeutics Development Center, National Jewish Health and lead Principal Investigator in the AEROW clinical trial, “By delivering copies of the CFTR∆R transgene to the lung epithelium with a novel aerosolized AAV and achieving high levels of CFTR protein expression in airway cells, 4D-710 has the potential to provide durable benefit in these individuals and potentially all individuals affected by CF.” “4D-710, our next generation aerosolized A101 vector, has the potential to address the limitations of prior aerosol gene therapies. Initial results from the AEROW study showed that 4D-710 resulted in CFTR expression in lung airways that significantly exceeded our target profile. Safety and pulmonary function measures reinforce a promising emerging tolerability and clinical activity profile,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “We are also excited to welcome Dr. Alan Cohen as our Pulmonology Therapeutic Area Head. Alan brings more than 30 years of broad pulmonology expertise including in cystic fibrosis, alpha-1 antitrypsin deficiency, idiopathic pulmonary fibrosis, plus biotherapeutics and gene editing development, highlighting our commitment to pulmonology. Under Alan’s leadership, we expect to continue advancing the clinical development of 4D-710 for CF lung disease and 4D-725 for alpha-1 antitrypsin deficiency lung disease and future lung programs.” “The high CFTR expression levels and durable clinical activity of 4D-710 as demonstrated by improvements in quality of life and stability in ppFEV1 through 12 months in Cohort 1 have never been achieved with any gene delivery in CF, making a dose reduction feasible,” said Alan Cohen, M.D., SVP, Therapeutic Area Head of Pulmonology of 4DMT. “I’m excited to work closely with the CF Foundation, CF community, and regulatory agencies to advance the development of 4D-710, a potentially transformative medicine for people with CF. Given the efficiency we have observed in CF lungs, one of the most difficult organs for gene delivery vectors, I am also energized by the potential of A101 to deliver genetic payloads to treat multiple large-market pulmonology diseases including alpha-1 antitrypsin deficiency lung disease.” Data below is from Cohort 1 (1E15 vg, n=3) and Cohort 2 (2E15 vg, n=4) of the ongoing Phase 1/2 AEROW trial. Safety: Generally Well-Tolerated Acute safety (during and up to 4 h post dosing): Generally well tolerated, no clinically significant adverse events (AEs); no decrease in ppFEV1 (percent predicted forced expiratory volume in 1 second) or bronchospasm reported Post-dosing safety (follow-up in 7 participants through 4-17 months); best available as of October 2023: Generally well-tolerated No inflammation observed in biopsies collected to date in all 7 participants No related AEs in 6 of 7 patients at any timepoint Single SAE (participant 3 of 4 dosed in Cohort 2; pneumonitis not otherwise specified): Serious due to hospitalization (<72 hours). High-resolution computed tomography (hospital radiologist reading) reported differential diagnosis as “atypical infection, cryptogenic organizing pneumonia.” Following discharge, lung lavage bacterial cultures confirmed Inquilinus limosus infection. Participant was treated with oral steroids and outpatient IV antibiotics, and AE subsequently resolved. AE consistent with bacterial pneumonia (Inquilinus limosus). Principal Investigator reported as possibly related to 4D-710 Lung Tissue Biomarkers: Expression Significantly Exceeded Target Pro All Patients Robust and reproducible 4D-710-mediated CFTR protein (by immunohistochemistry, IHC) and RNA (by in situ hybridization, ISH) expression observed in airway epithelium 4-8 weeks following aerosol delivery in all 7 participants across all 34 airway biopsy and brushing samples collected CFTR protein detected in ~98% and ~99% of airway epithelial cells in samples from Cohort 1 and 2 participants, respectively versus ~44% of cells in normal control lung samples Mean CFTR protein expression levels by immunohistochemistry observed in Cohorts 1 and 2 participants were ~450% of levels in normal control lung samples, and ~1,000% of levels in control lung samples from individuals with CF All major airway cell types expressed CFTR protein and CFTR∆R RNA, including long-lived basal cells and secretory (Goblet) cells In situ hybridization (ISH) for RNA confirmed widespread, reproducible CFTR∆R transgene expression in all lung samples evaluated in all participants; positive signal observed in 40% and 53% of airway epithelial cells in samples from Cohort 1 and 2 participants, respectively. More cells were positive by IHC than by ISH Biomarker Lung Biopsy Measure* Control (Normal Lung) (n=10 biopsy samples) Control (CF Lung) (n=35 biopsy samples) Cohort 1 (1E15 vg, n=5 biopsy samples) Cohort 2 (2E15 vg, n=8 biopsy samples) CFTR Protein Expression (by IHC) Mean (range) % of airway cells (+) 44% (17-73%) 18% (1-62%) 98% (93-100% >99%** (99-100%) Mean (Range) Intensity (H-Score) 47 (17-75) 19 (1-68) 205 (133-253) 225** (143-280) * ISH and IHC scoring performed with machine learning-assisted image analysis software (Visiopharm), with review and confirmation by independent certified M.D. pathologist masked to lung tissue source ** CFTR expression observed in Cohort 2 was not statistically significantly increased compared to Cohort 1 Cohort 1 Clinical Activity: Durable Through 12 Months and Beyond Clinical activity assessments collected through 12 months (amendment planned to collect additional follow-up data after 12 months): Participant with moderate lung impairment by ppFEV1 (n=1) Participants with mild/no lung impairment by ppFEV1 (n=2) Lung Function (ppFEV1) Absolute ∆ from baseline over 12 months +1% to +10% improvement Stable (±2%) Quality of Life (CFQ-R-RD*) ∆ from baseline over 12 months Mean increase of 8.4 to 11.1 points over 12 month period consistently above MCID (MCID=±4); all 3 participants consistently improved beyond MCID * Cystic Fibrosis Questionnaire-Revised respiratory domain symptom score MCID, minimal clinically important difference In all 3 participants, no pulmonary exacerbations were reported beyond 3 months through up to 17 months of follow-up Cohort 2 clinical activity pending following additional follow-up (consistent with Cohort 1 clinical activity reporting timeline) Next Steps for 4D-710 Clinical Development Cohort 1 dose level (1E15 vg) selected to continue into Phase 2 Dose ranging continues (5E14 – 2E15 vg) with lung biopsy CFTR expression pro above normal controls, demonstrating the feasibility of effective treatment at lower doses; first participant dosed in lower dose Cohort 3 (5E14 vg) Additional functional measures added to AEROW study following strong proof-of-concept for above normal CFTR expression in airways: high-resolution computed tomography (HRCT), lung clearance index (LCI), mucociliary clearance index (MCI), number & severity of bacterial pulmonary exacerbations FDA feedback on development plan for monotherapy & approved CF modulator combination regimens expected to be shared in Q1 2024 Next interim Phase 1 data update expected mid-2024 Increased Financial Commitment from Cystic Fibrosis Foundation (The CF Foundation) Brings Total Historical Commitment to Over $20 Million 4DMT has been supported by the CF Foundation since 2016, including a 2017 research agreement (“CF Foundation Agreement”) to discover and develop optimized next generation AAV vectors for use in genetic medicines targeting lung airway cells in people with CF In August 2023 the Company executed an amendment to the CF Foundation Agreement increasing the funding commitment under that agreement by $2.8 million to a total of $6.3 million, which covers anticipated spend for further development of our aerosolized lung epithelium gene delivery vectors In 2020 and 2021, the CF Foundation invested $14 million in 4DMT equity to support the development of 4D-710 Webcast Details: Title: 4D-710 Phase 1/2 AEROW Interim Clinical Data and Program Update Webcast and Q&A Date/Time: Wednesday, November 1, 2023 at 4:30 p.m. ET Registration: Link An archived copy of the webcast will be available for up to one year by visiting the “Investors & Media” section of the 4DMT website at the following link: . About 4D-710 and Cystic Fibrosis Lung Disease 4D-710 is comprised of our targeted and evolved next generation vector, A101, and a codon-optimized CFTR∆R transgene. 4D-710 has the potential to treat a broad range of people with cystic fibrosis, independent of the specific CFTR mutation, and is designed for aerosol delivery to achieve CFTR expression within lung airway epithelial cells. 4D-710 is being initially developed for the approximately 15% of people whose disease is not amenable to existing CFTR modulator medicines (based on variant-eligibility and/or drug intolerance) targeting the CFTR protein. In people with CFTR mutations whose disease is amenable to modulator medicines, the improvement in lung function is incomplete and is variable. We therefore expect to potentially develop 4D-710 in this broader population, as a single agent and/or in combination with CFTR modulator small molecule medicines. Cystic fibrosis is an inherited, progressive disease caused by mutations in the CFTR gene. It affects the lungs, pancreas, and other organs. According to the CF Foundation, nearly 40,000 people in the United States and more than 105,000 people worldwide are living with cystic fibrosis, with approximately 1,000 new cases of cystic fibrosis diagnosed in the United States each year. Lung disease is the leading cause of morbidity and mortality in people with cystic fibrosis. Cystic fibrosis causes impaired lung function, inflammation and bronchiectasis and is commonly associated with persistent lung infections and repeated exacerbations due to the inability to clear thickened mucus from the lungs. People with cystic fibrosis require lifelong treatment with multiple daily medications. The complications of the disease result in progressive loss of lung function and hospitalizations, and ultimately lead to end-stage respiratory failure. About 4DMT 4DMT is a genetic medicines company with three novel, highly targeted next generation AAV vectors currently in human clinical studies targeting multiple large market diseases in ophthalmology and pulmonology, plus other therapeutic areas. 4DMT seeks to unlock the full potential of genetic medicines using its proprietary invention platform, Therapeutic Vector Evolution, which combines the power of the Nobel Prize-winning technology, directed evolution, with approximately one billion synthetic AAV capsid-derived sequences to invent customized and evolved vectors for use in our product candidates. All of our vectors are proprietary to 4DMT and were invented at 4DMT, including the vectors utilized in our clinical-stage and preclinical pipeline product candidates: R100, A101, and C102. The Company is initially focused on five clinical-stage product candidates in three therapeutic areas for both rare and large market diseases: ophthalmology, pulmonology, and cardiology. The 4DMT customized and evolved vectors were invented with the goal of being delivered at relatively low doses through clinically routine, well-tolerated, and minimally invasive routes of administration, transducing diseased cells in target tissues efficiently, having reduced immunogenicity and, where relevant, having resistance to pre-existing antibodies. 4DMT is currently advancing five product candidates in clinical development: 4D-150 for wet AMD and DME, 4D-710 for cystic fibrosis lung disease, 4D-310 for Fabry disease cardiomyopathy, 4D-125 for XLRP, and 4D-110 for choroideremia. The 4DMT preclinical product candidates in development are: 4D-175 for geographic atrophy and 4D-725 for AATLD. 4D-150, 4D-710, 4D-310, 4D-125, and 4D-110 are our product candidates in clinical development and have not yet been approved for marketing by the US FDA or any other regulatory authority. No representation is made as to the safety or effectiveness of 4D-150, 4D-710, 4D-310, 4D-125, or 4D-110 for the therapeutic uses for which they are being studied. 4D Molecular Therapeutics™, 4DMT™, Therapeutic Vector Evolution™, and the 4DMT logo are trademarks of 4DMT. Forward Looking Statements: This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding the therapeutic potential, and clinical benefits of 4DMT’s product candidates, as well as the plans, announcements and related timing for the clinical development of and regulatory interactions regarding 4D-710 and 4D-725. The words "may," “might,” "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," “expect,” "estimate," “seek,” "predict," “future,” "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including risks and uncertainties that are described in greater detail in the section entitled "Risk Factors" in 4D Molecular Therapeutics’ most recent Quarterly Report on Form 10-Q as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent 4D Molecular Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. 4D Molecular Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward looking statements. Contacts: Media: Katherine Smith Evoke Canale Katherine.Smith@evokegroup.com Investors: Julian Pei Head of Investor Relations and Corporate Communications jpei@4dmt.com 267-644-5097

Up to 60,000 patients in the United States may have PPF, with only one approved therapy available SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)-- United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, announced today that the first patient has enrolled in the registration-phase TETON PPF study, which will evaluate nebulized Tyvaso® (treprostinil) Inhalation Solution in 698 adult patients with progressive pulmonary fibrosis (PPF). This is in addition to two separate ongoing registration-phase studies, TETON 1 and TETON 2, of nebulized Tyvaso in patients with another type of pulmonary fibrosis (PF) known as idiopathic pulmonary fibrosis (IPF). The 52-week study will evaluate the impact of nebulized Tyvaso on a key prognostic indicator for PPF known as forced vital capacity (FVC). PPF is a progressive form of interstitial lung disease (ILD) characterized by the loss of the ability of the lungs to transfer oxygen into the blood, ultimately resulting in respiratory failure and death. Nebulized Tyvaso is currently approved by the U.S. Food and Drug Administration (FDA) to treat both pulmonary arterial hypertension and pulmonary hypertension (PH) associated with interstitial lung disease (PH-ILD). The PH-ILD indication, which includes patients with PH associated with IPF and PPF, was added to the nebulized Tyvaso label in March 2021 based on the successful results of the INCREASE study. Nebulized Tyvaso is only approved for use for PPF patients who may also have documented PH, to improve exercise capacity. The TETON PPF study seeks to evaluate the use of nebulized Tyvaso in PPF patients irrespective of whether or not they have PH. “The progressive pulmonary fibrosis phenotype represents a group of ILD patients who only have limited treatment options currently available to them,” said Steven Nathan, M.D., Medical Director of the Advanced Lung Disease and Lung Transplant Program at Inova Fairfax Hospital in Falls Church, Virginia, who is also chair of the TETON program steering committee. “The broader ILD data set from the INCREASE study showed improvements in FVC beyond just IPF patients, and the data provide the foundation for further study of inhaled treprostinil’s anti-fibrotic and disease modifying mechanism of action in patients with other forms of fibrotic lung disease like PPF.” “The initiation of the global TETON PPF study illustrates confidence in nebulized Tyvaso as a potential treatment option for patients with fibrotic lung disease,” said Natalie Breytenbach, Pharm.D., Associate Director, Global Product Development at United Therapeutics and the company’s lead for the TETON PPF study. “The expansion of TETON into the PPF patient population allows us to continue to evaluate inhaled treprostinil’s potential for treating this vulnerable group of patients in a robust global pivotal study.” The TETON program in IPF and PPF was prompted by data from the INCREASE study of nebulized Tyvaso for the treatment of PH-ILD, which demonstrated improvements in certain key parameters of lung function in pulmonary hypertension patients with fibrotic lung disease (improved absolute FVC and reduced exacerbations of underlying lung disease). Specifically, in the INCREASE study, treatment with nebulized Tyvaso resulted in significant improvements in percent predicted FVC at weeks 8 and 16, with subjects having an underlying etiology of IPF showing the greatest improvement (week 8: 2.5%; p=0.0380 and week 16: 3.5%; p=0.0147). In May 2022, data from the INCREASE open-label, long-term extension trial were presented at a medical conference, indicating that improvements in FVC were sustained for at least 64 weeks for PH-ILD patients with underlying IPF. For those patients who received placebo during the INCREASE study, marked improvements in FVC were observed following transition to nebulized Tyvaso during the open-label extension study. These data points, combined with substantial preclinical evidence of antifibrotic activity of treprostinil, suggest that nebulized Tyvaso may offer a treatment option for patients with IPF and PPF. Tyvaso DPI® (treprostinil) Inhalation Powder is not being evaluated in the TETON program, but United Therapeutics intends to seek FDA approval to expand the Tyvaso DPI label to include IPF and PPF, following completion of the TETON studies and any FDA-required bridging studies. About TETON PPF The TETON PPF study is a 698-patient, multicenter, randomized, double-blind, placebo-controlled phase 3 registration study to evaluate the safety and efficacy of nebulized Tyvaso in subjects with progressive pulmonary fibrosis (PPF) over a 52-week period. This third registration study is part of the global TETON program evaluating nebulized Tyvaso for the treatment of idiopathic pulmonary fibrosis (IPF) and PPF and will be conducted at sites globally. Subjects will be randomly allocated 1:1 to receive nebulized Tyvaso or placebo. All subjects will initiate nebulized Tyvaso or placebo at a dose of three breaths administered four times daily (QID) and will titrate to a target dosing regimen of 12 breaths QID. Study drug doses may be titrated up as tolerated, until the target dose or maximum clinically tolerated dose is achieved. The primary endpoint of the study is the change in FVC from baseline to week 52. Secondary endpoints include: (1) time to clinical worsening; (2) time to first acute exacerbation of interstitial lung disease (ILD); (3) overall survival at week 52; (4) change in percent predicted FVC from baseline to week 52; (5) change in the King’s Brief Interstitial Lung Disease questionnaire; and (6) change in the diffusing capacity of the lungs for carbon monoxide. Other data collected in the study will include the plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and supplemental oxygen use. Safety assessments include adverse event and serious adverse event monitoring, vital signs, clinical laboratory parameters, and electrocardiogram parameters. About PPF Progressive pulmonary fibrosis (PPF) is a group of interstitial lung disease (ILD) conditions that exhibit progressive, self-sustaining fibrosis, and display a similar disease course to idiopathic pulmonary fibrosis (IPF). PPF includes idiopathic interstitial pneumonias (other than IPF), autoimmune ILDs, chronic fibrosing hypersensitivity pneumonitis, and fibrotic ILDs related to environmental or occupational exposure. It is estimated that 13% to 40% of patients with these various ILDs will go on to develop PPF1. Patients with PPF exhibit decreased lung function, poor quality of life, and increased mortality despite usual treatments for the underlying ILD. Estimates for median transplant free survival and overall survival are approximately 2.9 years and 3.7 years, respectively.2,3 Further, United Therapeutics estimates there are up to 60,000 PPF patients in the United States. About Tyvaso® Inhalation Solution and Tyvaso DPI® Inhalation Powder INDICATION TYVASO (treprostinil) Inhalation Solution and TYVASO DPI (treprostinil) Inhalation Powder are prostacyclin mimetics indicated for the treatment of: Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies with TYVASO establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%). The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities. While there are long-term data on use of treprostinil by other routes of administration, nearly all clinical experience with inhaled treprostinil has been on a background of an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor. The controlled clinical experience with TYVASO was limited to 12 weeks in duration. Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study with TYVASO establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%). IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS TYVASO and TYVASO DPI are pulmonary and systemic vasodilators. In patients with low systemic arterial pressure, either product may produce symptomatic hypotension. Both products inhibit platelet aggregation and increase the risk of bleeding. Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness. Like other inhaled prostaglandins, TYVASO and TYVASO DPI may cause acute bronchospasm. Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm. Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with TYVASO and TYVASO DPI. DRUG INTERACTIONS/SPECIFIC POPULATIONS The concomitant use of either product with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension. Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8. Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality. There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production. Safety and effectiveness in pediatric patients have not been established. Across clinical studies used to establish the effectiveness of TYVASO in patients with PAH and PH‑ILD, 268 (47.8%) patients aged 65 years and over were enrolled. The treatment effects and safety pro in geriatric patients were similar to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy. ADVERSE REACTIONS Pulmonary Arterial Hypertension (WHO Group 1) In a 12-week, placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most common adverse reactions seen with TYVASO in ≥4% of PAH patients and more than 3% greater than placebo were cough (54% vs 29%), headache (41% vs 23%), throat irritation/pharyngolaryngeal pain (25% vs 14%), nausea (19% vs 11%), flushing (15% vs <1%), and syncope (6% vs <1%). In addition, adverse reactions occurring in ≥4% of patients were dizziness and diarrhea. In a 3-week, open-label, single-sequence, safety and tolerability study (BREEZE) conducted in 51 patients on stable doses of TYVASO who switched to a corresponding dose of TYVASO DPI, the most commonly reported adverse events seen with TYVASO DPI in ≥4% of PAH patients during the 3-week treatment phase included cough (35.3%), headache (15.7%), dyspnea (7.8%), and nausea (5.9%). Pulmonary Hypertension Associated with ILD (WHO Group 3) In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions with TYVASO were similar to the experience in studies of PAH. Please see Full Prescribing Information for TYVASO or TYVASO DPI, Instructions for Use manuals for TD-100 and TD-300 TYVASO® Inhalation System and TYVASO DPI™ Inhalation Powder, and additional information at or call 1‑877‑UNITHER (1-877-864-8437). TYVISIhcpMAY2022 United Therapeutics: Enabling Inspiration At United Therapeutics, our vision and mission are one. We use our enthusiasm, creativity, and persistence to innovate for the unmet medical needs of our patients and to benefit our other stakeholders. We are bold and unconventional. We have fun; we do good. We are the first publicly traded biotech or pharmaceutical company to take the form of a public benefit corporation. Our public benefit purpose is to provide a brighter future for patients through the development of novel pharmaceutical therapies; and technologies that expand the availability of transplantable organs. You can learn more about what it means to be a PBC here: unither.com/pbc. Forward-looking Statements Statements included in this press release that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, statements regarding the planned enrollment, conduct, and design of the TETON 1, TETON 2, and TETON PPF clinical studies, the potential for Tyvaso to become a treatment option for patients with fibrotic lung disease, our plans to seek IPF and PPF indications for the Tyvaso DPI label, and our goals of innovating for the unmet medical needs of our patients and to benefit our other stakeholders and furthering our public benefit purpose of developing novel pharmaceutical therapies and technologies that expand the availability of transplantable organs. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, that could cause actual results to differ materially from anticipated results. Consequently, such forward-looking statements are qualified by the cautionary statements, cautionary language and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of October 31, 2023, and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events, or any other reason. TYVASO and TYVASO DPI are registered trademarks of United Therapeutics Corporation. 1 Olson AL, Patnaik P, Hartmann N, et al. Prevalence and incidence of chronic fibrosing interstitial lung diseases with a progressive phenotype in the United States estimated in a large claims database analysis. Adv Ther. 2021;38:4100-4114. 2 Platenburg MGJP, van der Vis JJ, Grutters JC, van Moorsel CHM. Decreased survival and lung function in progressive pulmonary fibrosis. Medicina. 2023;59:296. 3 Cottin V, Teague R, Nicholson L, et al. The burden of progressive-fibrosing interstitial lung disease. Front Med. 2022;9:799912. View source version on businesswire.com: Contacts Dewey Steadman at (202) 919-4097 Source: United Therapeutics Corporation View this news release online at:

Bexmarilimab produces a 50% remission rate in doublet dose cohorts (11 out of 22 patients) Eight of the 11 patients are Complete Responders (CR) or CR with incomplete blood recovery (CRi) Highest overall response rate (ORR) of 80% observed in prior HMA-failure MDS group (4 out of 5 patients) Bexmarilimab continues to be well-tolerated with no dose-limiting toxicity observed Company to host virtual investor call to discuss data, today at 8:00 am EST Faron Pharmaceuticals Ltd. (AIM: FARN, First North: FARON), a clinical-stage biopharmaceutical company pioneering macrophage reprogramming for effective anticancer immunotherapies, today announces updated data from the Phase 1/2 BEXMAB study investigating bexmarilimab in combination with standard of care (SoC) in relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients having failed hypomethylating agents (HMAs). The updated data are consistent with the high objective response rate observed in the previous results. The most recent data includes read outs from a total of 22 patients (r/r AML with 12 patients, MDS frontline and MDS HMA-failed patients with five patients each) who have completed at least two or more treatment cycles. Eight of 11 patients achieved complete remission in the bone marrow with or without blood count recovery. The highest single indication-specific ORR was observed among HMA-failed MDS patients (4 out of 5 patients; 80%). The combined study ORR continues to be high (11 out of 22 patients; 50%) across all patient groups having received two or more treatment cycles in the doublet. In most patients (75%), blast reduction was observed. A total of 29 patients have been recruited into the doublet cohort as of October 5, 2023. Bexmarilimab continues to be well-tolerated at all tested dose levels as no dose-limiting toxicity has been observed. A total of 18 drug-related events were observed with the majority below Grade 3. Five drug-related events were reported as Grade 3 and above, including immune-related events (capillary leak syndrome, hemophagocytic lymphohistiocytosis and cryptogenic organizing pneumonia), as well as one event of increased liver enzymes. “The emerging data from Phase 1/2 continue to be extremely promising, showing continued good safety, encouraging efficacy and long durations of response,” said Dr. Markku Jalkanen, Chief Executive Officer of Faron. “These results strongly support the planned next step of beginning enrollment of the Phase 2 part of the BEXMAB study.” Dr. Jalkanen continued: “We believe that bexmarilimab has the potential to provide better patient outcomes and improve the quality of life of those suffering from relapsed/refractory AML and MDS, which are conditions with dire prognosis and limited new therapies in the last decades.” Faron plans to initiate the Phase 2 part of the BEXMAB study in HMA-failed MDS and r/r AML patients in Q4 2023. Consistent with the FDA’s Project Optimus initiative, the planned Phase 2 will start with dose optimization and is expected to enroll 28-32 patients randomized between two selected doses. Faron plans to increase the number of US clinical sites from two to five sites to accelerate study recruitment. For more information on BEXMAB, please visit ClinicalTrials.gov and reference Identifier NCT05428969. Faron will host a virtual call for investors to discuss the data today at 08.00 EST/13.00 BST/15.00 EEST. There will also be an opportunity to ask questions during the webcast. To register for the webcast, please visit: https://faron.videosync.fi/recent-bexmab-results-and-future-outlook-event or contact the IR team for more information at investor.relations@faron.com. About Bexmarilimab Bexmarilimab is Faron's wholly owned, investigational immunotherapy designed to overcome resistance to existing treatments and optimize clinical outcomes, by targeting myeloid cell function and igniting the immune system. Bexmarilimab binds to Clever-1, an immunosuppressive receptor found on macrophages leading to tumor growth and metastases (i.e. helps cancer evade the immune system). By targeting the Clever-1 receptor on macrophages, bexmarilimab alters the tumor microenvironment, reprogramming macrophages from an immunosuppressive (M2) state to an immunostimulatory (M1) one, upregulating interferon production and priming the immune system to attack tumors and sensitizing cancer cells to standard of care. About BEXMAB The BEXMAB study is an open-label Phase 1/2 clinical trial investigating bexmarilimab in combination with standard of care (SoC) in the aggressive hematological malignancies of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The primary objective is to determine the safety and tolerability of bexmarilimab in combination with SoC (azacitidine) treatment and to identify the recommended Phase II dose. Directly targeting Clever-1 could limit the replication capacity of cancer cells, increase antigen presentation, ignite an immune response, and allow current treatments to be more effective. Clever-1 is highly expressed in both AML and MDS and associated with therapy resistance, limited T cell activation and poor outcomes. About Faron Pharmaceuticals Ltd. Faron (AIM: FARN, First North: FARON) is a global, clinical-stage biopharmaceutical company, focused on tackling cancers via novel immunotherapies. Its mission is to bring the promise of immunotherapy to a broader population by uncovering novel ways to control and harness the power of the immune system. The Company’s lead asset is bexmarilimab, a novel anti-Clever-1 humanized antibody, with the potential to remove immunosuppression of cancers through targeting myeloid cell function. Bexmarilimab is being investigated in Phase I/II clinical trials as a potential therapy for patients with hematological cancers in combination with other standard treatments. Further information is available at www.faron.com. The content above comes from the network. if any infringement, please contact us to modify.