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|Item 8.01|| |
On June 14, 2021, Terns Pharmaceuticals, Inc. (the “Company” or “Terns”) announced positive top-line data from its Phase 2a LIFT trial of TERN-101 in NASH patients.
On June 14, 2021, the Company issued a press release and provided a corporate presentation relating to its topline results from its Phase 2a LIFT trial of TERN-101 in NASH patients. A copy of the press release and the presentation are filed as Exhibits 99.1 and 99.2 to this Current Report on Form 8-K and are incorporated herein by reference.
The information contained in the press release and the presentation is summary information that is intended to be considered in the context of the more complete information included in the Company’s filings with the U.S. Securities and Exchange Commission (the “SEC”) and other public announcements that the Company has made and may make from time to time. The Company undertakes no duty or obligation to update or revise the information contained in this report, although it may do so from time to time as its management believes is appropriate. Any such update may be made through the filing of other reports or documents with the SEC.
|Item 9.01|| |
Financial Statements and Exhibits
|99.1||Press Release, dated June 14, 2021|
|99.2||Company Presentation dated June 14, 2021|
|104||Cover Page Interactive Data File, formatted in inline XBRL.|
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|TERNS PHARMACEUTICALS, INC.|
|Date: June 14, 2021||By:|
Chief Operating Officer and General Counsel
Terns Reports Positive Top-line Results from Phase 2a LIFT Study of FXR Agonist TERN-101 in Patients with NASH
First FXR agonist trial to demonstrate no discontinuations due to AEs, including pruritus, and both a differentiated pruritus and lipid profile in patients with NASH
First 12-week controlled trial in patients with NASH to show significant improvements in corrected T1 (cT1), an imaging marker of liver inflammation and fibrosis linked to clinical outcomes
Terns plans to initiate first NASH trial of an FXR agonist (TERN-101) in combination with a THR-ß agonist (TERN-501) in 1H22
Company to host conference call and webcast at 8:30 a.m. ET today
FOSTER CITY, Calif., June 14, 2021 Terns Pharmaceuticals, Inc. (Terns or the Company) (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule single-agent and combination therapy candidates for the treatment of non-alcoholic steatohepatitis (NASH) and other chronic liver diseases, today reported positive top-line results from the Phase 2a LIFT clinical trial of TERN-101, a liver-distributed farnesoid X receptor (FXR) agonist for the treatment of patients with NASH.
The LIFT study is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase 2a clinical trial to evaluate the safety, tolerability, efficacy, and pharmacokinetics of orally-administered TERN-101 tablets at doses of 5 mg, 10 mg and 15 mg in 100 adult patients with presumed non-cirrhotic non-alcoholic steatohepatitis (NASH). The primary objective of the clinical trial was to evaluate the safety and tolerability of TERN-101 over 12 weeks of treatment plus a four-week post-treatment follow-up period. Secondary endpoints included percent change from baseline in ALT levels and plasma pharmacokinetics of TERN-101. Exploratory efficacy endpoints included changes in liver fibro-inflammation measured by MRI corrected T1 (cT1), liver fat content by MRI proton density fat fraction (MRI-PDFF), pharmacodynamic parameters, and serum NASH biomarkers.
In the LIFT trial, TERN-101 was generally well tolerated with a similar incidence of adverse events (AEs) across treatment groups. All treatment-related adverse events were mild/moderate with no apparent dose relationship. There were no treatment-related serious adverse events, and no patient discontinued TERN-101 due to any adverse event including pruritus. The most frequent treatment-emergent adverse events included pruritus, headache, constipation, diarrhea, decreased appetite and dizziness. Pruritus was reported in four patients (16%) in the 5 mg TERN-101 arm, three patients (11.5%) in the 10 mg TERN-101 arm, four patients (17.4%) in the 15 mg TERN-101 arm and no patients in the placebo group. Three pruritus cases were Grade 2 (widespread and intermittent); the rest were Grade 1 (mild or localized). Notably, there were no Grade 3 (widespread and constant) pruritus events and no discontinuations due to pruritus. Most pruritus cases resolved during continued TERN-101 treatment.
No change in LDL cholesterol was observed in patients in the 5 mg and 10 mg TERN-101 arms as compared to placebo (Week 12 mean change: 4.8% for placebo, 6.7% for 5 mg TERN-101, 3.2% for 10 mg TERN-101, not significant). Statistically significant LDL changes were observed only in the 15 mg arm (Week 12 mean change: 15.9%, p<0.05). Significant decreases in HDL cholesterol were observed in all TERN-101 dose groups at Week 4 and Week 8 but returned toward baseline in the 5 mg and 10 mg dose groups without differences from placebo at Week 12. Decreases in HDL were significantly different from placebo for the 15 mg group at all observed timepoints through Week 12.
Multiple efficacy biomarkers of NASH, including corrected T1 (cT1), MRI-PDFF and ALT, were evaluated in the LIFT Study:
Mean changes in cT1 at Week 12 were -0.8 msec for placebo, -38.0 msec (p=0.033) for the 5 mg arm, -57.7 msec (p=0.002) for the 10 mg arm, and -74.0 msec (p<0.001) for the 15 mg arm. Improvements of at least 80 msec in cT1 were observed in a significant proportion of patients in the 5 mg and 10 mg groups at Week 12 (as compared to placebo). Significant decreases in cT1 were also observed at Week 6 for all dose groups. cT1 is a magnetic resonance-based imaging test measuring free-water content in liver tissue, which has shown a strong correlation with inflammation and fibrosis histology and clinical outcomes in patients with liver disease.
Mean relative changes in MRI-PDFF were -8.4% (placebo), -15.1% (5 mg), -19.7% (10 mg), and -12.9% (15 mg) at Week 12. Mean relative changes in MRI-PDFF were significant at Week 6 for the 10 mg and 15 mg dose groups compared to placebo, although these changes were not statistically significant at Week 12. MRI-PDFF is an imaging marker that measures liver fat content.
Mean percent changes in ALT at Week 12 were -5.3% (placebo), -2.6% (5 mg), -18% (10 mg), and -13.2% (15 mg).
No discernable trends were observed in initial analyses of the enhanced liver fibrosis (ELF) score, CK-18 and Pro-C3.
NASH is a complex multifaceted condition, making it difficult to use just one target to treat the disease. The LIFT data are exciting because we see improvement in key non-invasive tests associated with disease severity along with an attractive safety profile with no discontinuations due to side effects, said Rohit Loomba, MD, MHSc, director of the UC San Diego NAFLD Research Center and director of Hepatology at UC San Diego School of Medicine. The results add to the growing body of evidence showing the promise of TERN-101 as a multi-modal therapy to treat the multiple facets of this disease.
Summary of Week 12 Analysis
|TERN-101 tablet formulation
MRI-PDFF relative change (%)
p<0.05, **p<0.01, ***p<0.001 versus placebo
cT1 was conducted only at available sites (n=22, 24, 20 and 18 for placebo, 5 mg, 10 mg and 15 mg groups, respectively).
We are encouraged by the positive effects of well tolerated doses of TERN-101 on cT1 relaxation time, a biomarker correlated with improved clinical outcomes. LIFT is the first controlled NASH trial to show significant cT1 improvement as early as Week 6. TERN-101 has the potential to be an effective component of a NASH treatment regimen. We look forward to advancing this program in our planned combination therapy trial, said Erin Quirk, MD, president, chief medical officer and head of research and development at Terns. I would like to thank all those who have helped us rapidly advance the LIFT Study, including our outstanding team of investigators and clinical sites, the members of the Terns team, and the patients who participated in the study.
Terns plans to submit data from the LIFT Study to an upcoming scientific conference. Based on these positive results, Terns continues to plan a combination trial of TERN-101 together with TERN-501, the Companys thyroid hormone receptor beta agonist (THR-ß) also in development for the treatment of NASH. The multiple ascending dose portion of the TERN-501 Phase 1 trial started in June 2021, and top-line data from the trial is expected in the second half of 2021. The combination trial of TERN-101 and TERN-501 is expected to start in the first half of 2022.
Investor Conference Call
Terns will host an update call for investors today, June 14, 2021, beginning at 8:30 a.m. ET. The webcast of the conference call will be made available at https://edge.media-server.com/mmc/p/2gsxxmta. To access the call via dial-in, please dial 1-833-665-0612 (U.S./Canada toll-free) or 1-929-517-0403 (international) using the conference code 7587739. A replay of the call will also be available on the investor page of the Terns website for 30 days.
TERN-101 is a liver-distributed, non-bile acid FXR agonist that has demonstrated a differentiated tolerability profile and improved target engagement, likely due to its sustained FXR activation in the liver but only transient FXR activation in the intestine. FXR is a nuclear receptor primarily expressed in the liver, intestine and kidneys. FXR regulates hepatic expression of various genes involved in lipid metabolism, inflammation and fibrosis. Clinical studies of other FXR agonists have demonstrated significant histological NASH improvements but have also resulted in pruritus, adverse lipid changes and discontinuations.
About Terns Pharmaceuticals
Terns Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing a portfolio of small-molecule single-agent and combination therapy candidates for the treatment of non-alcoholic steatohepatitis, or NASH, and other chronic liver diseases. Terns programs are based on clinically validated and complementary mechanisms of action to address the multiple hepatic disease processes of NASH in order to drive meaningful clinical benefits for patients. For more information, please visit www.ternspharma.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements about Terns Pharmaceuticals, Inc. (the Company, we, us, or our) within the meaning of the federal securities laws, including those related to the Companys therapeutic potential of TERN-101; the potential utility and progress of the Companys product candidates in NASH, including the clinical utility of the data from and the endpoints used in the Phase 2a LIFT Study of TERN-101; expectations of timing and potential results of the Companys clinical trials; the Companys clinical development plans and activities, including the development plans for TERN-101 in combination with TERN-501 and potentially other product candidates; the Companys expectations regarding the profile of its product candidates, including tolerability, safety, metabolic stability and pharmacokinetic profile; the Companys ability to continue to execute on its clinical strategy and plans; and the sufficiency of our cash on hand to fund our operating expenses and capital expenditures. All statements other than statements of historical facts contained in this press release, including statements regarding the Companys strategy, future financial condition, future operations, future trial results, projected costs, prospects, plans, objectives of management and expected market growth, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as aim, anticipate, assume, believe, contemplate, continue, could, design, due, estimate, expect, goal, intend, may, objective, plan, positioned, potential, predict, seek, should, target, will, would and other similar expressions that are predictions of or indicate future events
and future trends, or the negative of these terms or other comparable terminology. The Company has based these forward-looking statements largely on its current expectations, estimates, forecasts and projections about future events and financial trends that it believes may affect its financial condition, results of operations, business strategy and financial needs. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. These statements are subject to risks and uncertainties that could cause the actual results and the implementation of the Companys plans to vary materially, including the risks associated with the initiation, cost, timing, progress and results of the Companys current and future research and development activities and preclinical studies and clinical trials. In particular, the impact of the COVID-19 pandemic on the Companys ability to progress with its research, development, manufacturing and regulatory efforts, including the Companys clinical trials for its product candidates, will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements in the United States and in other countries, and the effectiveness of actions taken globally to contain and treat the disease. These risks are not exhaustive. For a detailed discussion of the risk factors that could affect the Companys actual results, please refer to the risk factors identified in the Companys SEC reports, including but not limited to its Annual Report on Form 10-K for the year ended December 31, 2020 and Quarterly Report on form 10-Q for the three months ended March 31, 2021. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements for any reason.
Contacts for Terns
Berry & Company Public Relations
TERNS PHARMACEUTICALS LIFT Study Topline Results A 12-Week Phase 2a Trial of TERN-101 in NASH Patients June 14th, 2021 NASDAQ: TERN
Forward-Looking Statements This presentation contains forward-looking statements about Terns Pharmaceuticals, Inc. (the Company, we, us, or our) and its industry that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding the Companys strategy, future financial condition, future operations, projected costs, prospects, plans, objectives of management and expected market growth or statements regarding the therapeutic potential of TERN-101, the clinical utility of the data from and the endpoints used in the Phase 2a LIFT Study of TERN-101 and potential clinical development plans for TERN-101 and the Companys other product candidates such as TERN-501, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as aim, anticipate, assume, believe, contemplate, continue, could, design, due, estimate, expect, goal, intend, may, objective, plan, positioned, potential, predict, seek, should, target, will, would and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. The Company has based these forward-looking statements largely on its current expectations, estimates, forecasts and projections about future events and financial trends that it believes may affect its financial condition, results of operations, business strategy and financial needs. In light of the significant uncertainties in these forwardlooking statements, you should not rely upon forward-looking statements as predictions of future events. Although the Company believes that it has a reasonable basis for each forward-looking statement contained in this presentation, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur at all. These risks are not exhaustive. For a detailed discussion of the risk factors that could affect our actual results, please refer to the risk factors identified in our SEC reports, including but not limited to our Annual Report on Form 10-Kforthe year ended December 31, 2020 and our Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2021. New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation. This presentation discusses product candidates that are investigational only and have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these product candidates for the use for which such product candidates are being studied. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. Acknowledgements ,fUFT Terns would like to acknowledge and thank the patients, investigators, and LIFT study team,
TfUFT Terns would like to acknowledge and thank theerns Pipeline: Designed to Address Multifaceted Nature of NASH Combining candidateswith complementary mechanisms to maximize NASH response rates patients, investigators, and LIT study team,
3LIFT 3 Important Firsts for NASH Treatment First FXR agonist trial to demonstrate no discontinuations due to AEs, including pruritus - TERN-101 was generally well-tolerated with similar incidence of AEs across treatment groups - No treatment-related SAEs First 12-week controlled trial in NASH to show significant improvements in cT1 - cT1 is an imaging marker of liver inflammation and fibrosis linked to clinical outcomes1 - Also observed improvements in PDFF and liver enzymes First NASH trial of an FXR agonist (TERN-101) in combination with a THR-p agonist (TERN-501) planned for 1H22 initiation - TERN-501 Phase 1 MAD portion started in June 2021 with data expected in 2H 2021 AE = adverse event. SAE = severe adverse event. FXR = farnesoid X receptor. NASH = nonalcoholic steatohepatitis. THR=thyroid hormone receptor 1. Liver International. 2020;40:3071-3082
Terns Pipeline: Designed to Address Multifaceted Nature of NASH Combining candidates with complementary mechanisms to maximize NASH respo nse rates
TERN-101: A Differentiated Liver-Distributed FXR Agonist
^LIFT Phase 2a Trial in Patients with NASH Primary objective: Safety assessment Secondary /exploratory objectives: ALT, PK, cT1, MRI-PDFF, and other biomarkers Randomized, Double Blind NAH patients based on clinical characteristics or prior biopsy with fibrosis but not cirrhosis
Exploratory Endpoints Include Multi-parametric MR Imaging: MRI-PDFF & Corrected T1 (cT1)
cT1 is Correlated with Liver Histology Both PDFF and cT1 correlated with NAS, but only cT1 correlates with fibrosis cT1 was also correlated with fibrosis and was superior to PDFF for detection of fibrosis and inflammation Source: Dennis, et al 2021 Front. Endocrinol. 1. Mean cT1 baseline range of LIFT patients
Patient Disposition: High Rate of Completion No patient discontinued TERN-101 or placebo due to adverse events including pruritus
Baseline Characteristics: Balanced Across Treatment Arms Representative of High-risk F2/F3 NASH Population
Primary Objective Safety Summary: Well Tolerated with No Discontinuations Due to Any AE No treatment-related serious adverse events were observed
Most Frequent Treatment-Emergent Adverse Events All treatment-related AEs were mild/moderate with no apparent dose-relationship Pruritus: no Grade 3; no discontinuations; most resolved with continued dosing
Minimal Lipid Changes in TERN-101 5mg and 10mg Cohorts
ALT: Mean % Change (SE) from Baseline AST: Mean % Change (SE) from Baseline GGT: Mean % Change (SE) from Baseline SE = Standard error 15 ALP: Mean % Change (SE) from Baseline
Improvement in Liver Fat Content (MRI-PDFF) MRI-PDFF Mean Relative Change (SE) from Baseline [%] Week 12
^LIFT is the First Trial in NASH Patients to Show Significant Improvements in cT1 Starting as Early as 6 Weeks cT1 Mean Change (SE) from Baseline [msec] TERNS PHARMACEUTICALS
Substantially More Patients in Each TERN-101 Cohort Had Improvements in cT1 % with > 80 msec 18 decline at Week 12
^LIFT Patient Case Studies: Changes in cT1
cT1 is Significantly Correlated with Clinical Outcomes cT1 and Histology Have Shown Equivalent Performance for Predicting Clinical Outcomes cT1, but not MRI-PDFF, correlated with clinical outcomes
cT1 Results in Context of Late-Stage NASH Investigational Products TERN-101 cT1 changes comparable to late-stage development candidates
cT1 Results in Context of Late-Stage NASH Investigational Products TERN-101 cT1 changes comparable to late-stage development candidates
3LIFT 3 Important Firsts for NASH Treatment First FXR agonist trial to demonstrate no discontinuations due to AEs, including pruritus TERN-101 was generally well-tolerated with similar incidence of AEs across treatment groups No treatment-related SAEs First 12-week controlled trial in NASH to show significant improvements in cT1 cT1 is an imaging marker of liver inflammation and fibrosis linked to clinical outcomes1 Also observed improvements in PDFF and liver enzymes First NASH trial of an FXR agonist (TERN-101) in combination with a THR-p agonist (TERN-501) planned for 1H22 initiation - TERN-501 Phase 1 MAD portion started in June 2021 with data expected in 2H 2021 AE = adverse event. SAE = severe adverse event. FXR = farnesoid X receptor. NASH = nonalcoholic steatohepatitis. THR=thyroid hormone receptor 1. Liver International. 2020;40:3071-3082
Terns Pipeline: Multiple Catalysts Over the Next 12 Months Combining candidates with complementary mechanisms to maximize NASH patient benefit
Key Completed and Upcoming Milestones Multiple clinical milestones in 2021/2022 in preparation for combo trials
TERN-501: Differentiated THR-0 AgonistTHR-p regulates key aspects of energy metabolism (e.g., fatty acid & lipid synthesis, liver fat removal through fatty acid oxidation) TERN-501 is a selective Thyroid Hormone Receptor beta (THR-p) agonist with enhanced metabolic stability and liver distribution Other THR-p agonists face limitations with off- target effects or unpredictable PK due to CYP metabolism TERN-501 was screened for greater selectivity and enhanced metabolic and PK stability - Expected low clinical dose - Attractive for monotherapy or combination therapy Phase 1 SAD/MAD
TERN-501: Improved PK & THR-0 Selectivity Differentiated and excellent candidate for co-formulation TERN-501: Improved Pharmacokinetics
TERN-501: Single Dose Suppresses Cholesterol Improved potency relative to resmetirom
I TERN-501 Activity in DIO/CCI4 NASH Model I Liver histology, liver function, lipid parameter improvements
TERN-101+TERN-501 Combination NASH Model Combination shows additional effects on steatosis and fibrosis improvement