We are a clinical-stage biopharmaceutical company dedicated to the identification, development and commercialization of differentiated medicines to address the unmet medical needs of patients with cancers.
−Removed: We seek to utilize our team’s deep drug development experience to maximize the potential of our lead development candidate, furmonertinib, and advance a pipeline of novel therapeutics, such as next-generation antibody drug conjugates, through approval and commercialization in patients suffering from cancer, with an initial focus on solid tumors.
−Removed: Furmonertinib is currently being evaluated in multiple clinical trials across a range of epidermal growth factor receptor (EGFR) mutations (EGFRm) in non-small cell lung cancer (NSCLC), including a pivotal Phase 3 clinical trial in treatment naive, or first-line, patients with locally advanced or metastatic EGFRm NSCLC with exon 20 insertion mutations.
−Removed: We received Breakthrough Therapy Designation for furmonertinib for this disease from the U.S.
−Removed: Food and Drug Administration (FDA) in October 2023 , and Orphan Drug Designation for treatment of NSCLC with EGFRm or human epidermal growth factor receptor 2 (HER2) mutations or HER4 mutations in February 2024 .
+Added: We seek to utilize our team’s deep drug development experience to maximize the potential of our lead development candidate, firmonertinib, and advance a pipeline of novel therapeutics, such as next-generation antibody drug conjugates, through approval and commercialization in patients suffering from cancer, with an initial focus on solid tumors.
+Added: Firmonertinib is currently being evaluated in multiple clinical trials across a range of epidermal growth factor receptor (EGFR) mutations (EGFRm) in non-small cell lung cancer (NSCLC), including a pivotal Phase 3 clinical trial in treatment naive, or first-line, patients with locally advanced or metastatic EGFRm NSCLC with exon 20 insertion mutations.
+Added: We received Breakthrough Therapy Designation for firmonertinib for this disease from the U.S.
+Added: Food and Drug Administration (FDA) in October 2023 , and Orphan Drug Designation for treatment of NSCLC with EGFRm or human epidermal growth factor receptor 2 (HER2) mutations or human epidermal growth factor receptor 4 (HER4) mutations in February 2024 .
A product candidate can receive Breakthrough Therapy Designation if preliminary clinical evidence indicates that the product candidate, alone or in combination with one or more other drugs, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
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The receipt of a Breakthrough Therapy Designation for a product candidate may not result in a faster development process, review or approval compared to product candidates considered for approval under conventional FDA procedures and does not increase the likelihood that the product candidate will ultimately receive FDA approval for any indication.
−Removed: Furmonertinib is an investigational, novel, EGFR mutant-selective tyrosine kinase inhibitor (TKI) that we are developing for the treatment of NSCLC patients across a broader set of EGFR mutations (EGFRm) than are currently served by approved EGFR TKIs.
−Removed: Furmonertinib is currently only approved and commercially distributed by Shanghai Allist Pharmaceuticals Company, Ltd.
−Removed: (Allist) in China as a first-line therapy to treat classical EGFRm NSCLC.
−Removed: The FDA has not approved furmonertinib for any use.
−Removed: We selected furmonertinib for global development against nonclassical, or uncommon, mutations based on preliminary reductions in tumor size activity observed in seven out of ten patients in first-line treatment with EGFR exon 20 insertion mutations in the ongoing Phase 1b clinical trial, the FAVOUR trial, conducted by Allist in China, and preclinical activity in P-loop and-alpha-c-helix compressing (PACC) mutations, each a subtype of uncommon mutation.
−Removed: In a subsequent interim data readout from the FAVOUR trial of furmonertinib in first-line patients with locally advanced or metastatic EGFRm NSCLC with exon 20 insertion mutations, 79% of patients (n=22 out of 28 patients) were observed to experience a reduction in tumor size of at least 30%.
−Removed: Allist expects to release final results of the primary analysis from the FAVOUR study in 2024.
−Removed: If the future clinical trial results of the FAVOUR trial are unfavorable, our clinical development plans for furmonertinib, which include conducting our global, pivotal Phase 3 FURVENT clinical trial in first-line non-squamous locally advanced or metastatic EGFRm NSCLC patients with exon 20 insertion mutations, may be adversely affected.
−Removed: In 2021, we licensed from Allist the right to develop and commercialize furmonertinib worldwide, with the exception of greater China, which includes mainland China, Hong Kong, Macau and Taiwan.
+Added: In 2021, we licensed from Shanghai Allist Pharmaceuticals, Co.
+Added: Ltd (Allist) the right to develop and commercialize firmonertinib worldwide, with the exception of greater China, which includes mainland China, Hong Kong, Macau and Taiwan.
+Added: Firmonertinib is an investigational, novel, EGFR mutant-selective tyrosine kinase inhibitor (TKI) that we are developing for the treatment of NSCLC patients across a broader set of EGFR mutations (EGFRm) than are currently served by approved EGFR TKIs.
+Added: Firmonertinib is currently only approved and commercially distributed by Allist in China as a first-line therapy to treat classical EGFRm NSCLC.
+Added: The FDA has not approved firmonertinib for any use.
+Added: We selected firmonertinib for global development against nonclassical, or uncommon, mutations based on preliminary reductions in tumor size activity observed in seven out of ten patients in first-line treatment with EGFR exon 20 insertion mutations in the ongoing Phase 1b clinical trial, the FAVOUR trial, conducted by Allist in China, and preclinical activity in P-loop and-alpha-c-helix compressing (PACC) mutations, each a subtype of uncommon mutation.
+Added: In a subsequent interim data readout from the FAVOUR trial of firmonertinib administered at 240 mg once daily in first-line patients with locally advanced or metastatic EGFRm NSCLC with exon 20 insertion mutations, 79% of patients (n=22 out of 28 patients) were observed to experience a reduction in tumor size of at least 30%.
As one of the most prevalent cancers in the world, lung cancer imposes a significant global burden on human health, and EGFRm NSCLC represents a significant proportion of those affected.
Despite progress in the therapeutic landscape for EGFRm NSCLC, many patients, particularly those with uncommon mutations, such as exon 20 insertions or PACC mutations, are underserved by existing treatments.
−Removed: In an interim data readout from the FAVOUR trial of furmonertinib in first-line patients with locally advanced or metastatic EGFRm NSCLC with exon 20 insertion mutations, 79% of patients (n=22 out of 28 patients) were observed to experience a reduction in tumor size of at least 30% from the baseline in a patient without evidence of progression as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
+Added: In an interim data readout from the FAVOUR trial of firmonertinib administered at 240 mg once daily in first-line patients with locally advanced or metastatic EGFRm NSCLC with exon 20 insertion mutations, 79% of patients (n=22 out of 28 patients) were observed to experience a reduction in tumor size of at least 30% from the baseline in a patient without evidence of progression as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
This measurement of reduction is the threshold in this trial for a partial response and for inclusion in determination of the overall response rate (ORR), which is the primary endpoint of this trial.
In the same interim data readout, those 79% of patients were observed to experience a 15.2 month median duration of response (DOR).
−Removed: results may not be indicative of final results;
−Removed: however, we believe these interim clinical results underscore furmonertinib’s potential in patients whose tumors contain an uncommon EGFRm.
+Added: Interim results may not be indicative of final results;
+Added: however, we believe these interim clinical results underscore firmonertinib’s potential in patients whose tumors contain an uncommon EGFRm.
We are currently conducting a pivotal Phase 3 clinical trial, the FURVENT clinical trial, in first-line locally advanced or metastatic non-squamous EGFRm NSCLC patients with exon 20 insertion mutations and we expect topline data from this trial in 2025.
−Removed: Additionally, we are conducting a Phase 1b clinical trial, the FURTHER clinical trial, in NSCLC patients with activating EGFRm, including a cohort with PACC mutations which has been fully enrolled, and we expect proof of concept data for this cohort in 2024.
−Removed: Subject to review of data and regulatory feedback, we intend to expand this Phase 1b clinical trial into a potentially registrational clinical trial for EGFRm NSCLC patients with PACC mutations.
+Added: Additionally, we are conducting a Phase 1b clinical trial, the FURTHER clinical trial, in NSCLC patients with activating EGFRm, including a cohort with PACC mutations.
+Added: In September 2024, we reported 64% of patients (n=14 out of 22 1L patients at 240mg) were observed to experience a confirmed reduction in tumor size of at least 30% from the baseline without evidence of progression as measured by RECIST 1.1 criteria .
Since our inception in 2021, we have assembled a robust oncology pipeline by leveraging our global network and our experience in business development transactions.
−Removed: In 2021, we licensed from Allist the right to develop and commercialize furmonertinib worldwide, with the exception of greater China, which includes mainland China, Hong Kong, Macau and Taiwan.
+Added: In 2021, we licensed from Allist the right to develop and commercialize firmonertinib worldwide, with the exception of greater China, which includes mainland China, Hong Kong, Macau and Taiwan.
+Added: Also in 2021, we entered into a research collaboration, as amended, with Aarvik Therapeutics, Inc.
+Added: (Aarvik) to leverage its proprietary multi-target, multivalent, site-specific conjugation antibody platform to discover next-generation antibody drug conjugates (ADCs) with improved activity and safety over single target bivalent ADCs.
+Added: In 2024, we entered into a collaboration agreement with Jiangsu Alphamab Biopharmaceuticals Co., Ltd.
+Added: (Alphamab), a wholly owned subsidiary of Alphamab Oncology, to discover, develop and commercialize novel ADCs for the treatment of cancers globally, with the exception of greater China, which includes mainland China, Hong Kong, Macau and Taiwan.
+Added: In January 2025, we entered into an exclusive license agreement with Lepu Biopharma Co.
+Added: (Lepu Biopharma) pursuant to which Lepu Biopharma granted us the right to develop and commercialize ARR-217 (MRG-007), an ADC for gastrointestinal cancers outside greater China, which includes mainland China, Hong Kong, Macau, and Taiwan.
We plan to continue to engage in business development activities to source additional innovative therapeutics in areas currently underserved by approved therapies.
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P-loop alpha-c helix compressing;
−Removed: Shanghai Allist Pharmaceuticals Company, Ltd.;
−Removed: Beijing InnoCare Pharma Tech Co., Ltd.;
−Removed: Aarvik Therapeutics, Inc.;
+Added: tyrosine kinase inhibitor;
+Added: Breakthrough Therapy Designation;
+Added: gastrointestinal tumors;
+Added: IND-enabling studies:
+Added: Investigational New Drug enabling studies;
+Added: new molecular entity;
First-line therapy;
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SHP2 inhibitor.
−Removed: The investigation of furmonertinib for the first-line treatment of NSCLC EGFR exon 20 insertion mutations is based on the ongoing FAVOUR Phase 1b study conducted by Allist and the ongoing FURVENT Phase 3 study.
−Removed: These studies are not yet complete, and no Phase 2 study has been conducted for this indication.
−Removed: The ongoing FURTHER Phase 1b study investigating furmonertinib for the treatment of EGFRm NSCLC includes cohorts with PACC mutations (first-line or greater) and exon 20 insertion mutations (second-line or greater).
−Removed: The evaluation of furmonertinib in combination with SHP2i for the second-line or greater treatment of EGFRm NSCLC is based on the ongoing Phase 1b study in collaboration with InnoCare.
+Added: The investigation of firmonertinib for the first-line treatment of NSCLC EGFR exon 20 insertion mutations is based on the ongoing FAVOUR Phase 1b study conducted by Allist and the ongoing FURVENT Phase 3 study.
+Added: These studies are not yet complete, and no Phase 2 study has been conducted for firmonertinib for the first-line treatment of NSCLC EGFR exon 20 insertion mutations.
+Added: The ongoing FURTHER Phase 1b study investigating firmonertinib for the treatment of EGFRm NSCLC includes cohorts with PACC mutations (first-line or greater) and exon 20 insertion mutations (second-line or greater).
+Added: The evaluation of firmonertinib in combination with SHP2i for the second-line or greater treatment of EGFRm NSCLC is based on the ongoing Phase 1b study in collaboration with InnoCare.
Currently approved EGFR TKIs have achieved considerable commercial success and have become the standard of care for patients with NSCLC with classical EGFRm which comprise approximately 69% of all EGFRm NSCLC patients.
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This unmet need leaves many EGFRm NSCLC patients with few effective treatment options.
−Removed: Furmonertinib is currently approved and commercially distributed by Allist in China as a first-line therapy to
−Removed: treat classical EGFRm NSCLC.
−Removed: However, furmonertinib was designed to have strong inhibitory activity, not only against classical EGFRm, but also against uncommon EGFRm, such as exon 20 insertion and PACC mutations which together account for approximately 22% of EGFRm NSCLC.
−Removed: To date, furmonertinib has been evaluated in multiple clinical trials with an aggregate patient population of over 700 patients against a broad range of EGFRm NSCLC, including both classical and uncommon EGFRm.
−Removed: Based on the results of preclinical and clinical trials conducted to date, we believe that furmonertinib has the potential to retain many of the key advantages of third-generation EGFR TKIs compared to first- and second-generation EGFR TKIs, including overcoming T790M mutations that confer resistance, while also targeting a broader set of EGFRm.
−Removed: In 2022, Allist first reported the results of its FURLONG clinical trial, a double blind, placebo-controlled Phase 3 clinical trial of furmonertinib in first-line NSCLC patients with classical EGFRm.
−Removed: In FURLONG, furmonertinib was compared with the first-generation EGFR TKI, gefitinib, and demonstrated superior progression free survival (PFS) over gefitinib, showing a median PFS of 20.8 months versus 11.1 months for gefitinib.
−Removed: Furmonertinib’s ability to cross the blood-brain barrier was also demonstrated in this clinical trial with a central nervous system (CNS) metastases specific ORR, which measured reduction of tumor size of at least 30% in brain metastases if present at the start of therapy, of 91% versus 65% for gefitinib.
−Removed: Based on observed clinical activity against exon 20 insertions in the FAVOUR clinical trial and observed activity against PACC mutations in preclinical studies, we believe furmonertinib is potentially differentiated from third-generation EGFR TKIs approved for classical EGFRm NSCLC.
−Removed: In the United States and the European Union, standard of care for first-line therapy in EGFRm NSCLC involving exon 20 insertion mutations is platinum-based chemotherapy with pemetrexed, which has significantly lower response rates and DOR compared to results achieved in first-line patients with classical EGFRm who can be treated with approved third-generation EGFR TKIs.
+Added: Firmonertinib is currently approved and commercially distributed by Allist in China as a first-line therapy to treat classical EGFRm NSCLC.
+Added: However, firmonertinib was designed to have strong inhibitory activity, not only against classical EGFRm, but also against uncommon EGFRm, such as exon 20 insertion and PACC mutations which together account for approximately 22% of EGFRm NSCLC.
+Added: To date, firmonertinib has been evaluated in multiple clinical trials with an aggregate patient population of over 1,000 patients against a broad range of EGFRm NSCLC, including both classical and uncommon EGFRm.
+Added: Based on the results of preclinical and clinical trials conducted to date, we believe that firmonertinib has the potential to retain many of the key advantages of third-generation EGFR TKIs compared to first- and second-generation EGFR TKIs, including overcoming T790M mutations that confer resistance to earlier generation TKIs, while also targeting a broader set of EGFRm.
+Added: In 2022, Allist reported the results of its FURLONG clinical trial, a double blind, placebo-controlled Phase 3 clinical trial of firmonertinib in first-line NSCLC patients with classical EGFRm.
+Added: In FURLONG, firmonertinib was compared with the first-generation EGFR TKI, gefitinib, and demonstrated superior progression free survival (PFS) over gefitinib, showing a median PFS of 20.8 months versus 11.1 months for gefitinib.
+Added: Firmonertinib’s ability to cross the blood-brain barrier was also demonstrated in this clinical trial with a central nervous system (CNS) metastases specific ORR, which measured reduction of tumor size of at least 30% in brain metastases if present at the start of therapy, of 91% versus 65% for gefitinib.
+Added: Based on observed clinical activity against exon 20 insertions in the FAVOUR clinical trial and observed activity against PACC mutations in preclinical studies, we believe firmonertinib is potentially differentiated from third-generation EGFR TKIs approved for classical EGFRm NSCLC.
+Added: In the United States and the European Union, standard of care for first-line therapy in EGFRm NSCLC involving exon 20 insertion mutations is platinum-based chemotherapy with pemetrexed with or without amivantamab.
+Added: These regimens have significantly lower response rates and DOR compared to results achieved in first-line patients with classical EGFRm who can be treated with approved third-generation EGFR TKIs.
Over 9% of EGFRm NSCLC patients are estimated to have exon 20 insertion mutations.
−Removed: Two EGFR-targeted therapies, mobocertinib (EXKIVITY ® ) and amivantamab (RYBREVANT ® ), are approved in the United States for previously treated EGFRm NSCLC patients with exon 20 insertion mutations.
−Removed: However, both drugs lack sufficient brain penetrance to effectively treat brain metastasis.
−Removed: In addition, mobocertinib has considerable safety and tolerability drawbacks.
−Removed: In October 2023, Takeda announced it is working with the FDA towards a voluntary withdrawal of mobocertinib in the United States , and intends to similarly initiate voluntary withdrawal globally, for patients with EGFR exon 20 insertion mutation-positive locally advanced or metastatic NSCLC whose disease has progressed on or after platinum-based chemotherapy.
−Removed: Furthermore, amivantamab is an intravenously administered biologic with high administration burden.
−Removed: We believe furmonertinib, if approved, has the potential to become a chemotherapy-free oral regimen in first-line EGFRm NSCLC patients with exon 20 insertion mutations given the clinical data generated in this patient population to date.
+Added: However, amivantimab lacks brain penetrance to effectively treat brain metastasis.
+Added: In March 2024 and July 2024, amivantamab in combination with chemotherapy, was approved in the United States and Europe, respectively, for first line EGFRm NSCLC patients with exon 20 insertion mutations.
+Added: However, amivantamab is an intravenously administered biologic lacking the advantages of oral therapies.
+Added: Furthermore, amivantamab is being dosed in combination with chemotherapy in this setting with chemotherapy associated toxicities.
+Added: We believe firmonertinib, if approved, has the potential to become a chemotherapy-free oral regimen in first-line EGFRm NSCLC patients with exon 20 insertion mutations given the clinical data generated in this patient population to date.
Guidelines employing TKIs for the treatment of many of the PACC-specific EGFRm are not established and, as a result, chemotherapy is often used as the default course of therapy, offering limited efficacy and introducing chemotherapy-related toxicity.
Afatinib (GILOTRIF ® ), a second-generation TKI, is also used in some patients, but has a poor safety profile and is not brain penetrant.
+Added: Osimertinib is frequently used in some patients, but the activity of osimertinib is much less than in classical EGFRm NSCLC.
Over 12% of EGFRm NSCLC patients are estimated to have PACC mutations.
−Removed: If approved, we believe furmonertinib has the potential to become a leading treatment option for first-line EGFRm NSCLC patients with PACC mutations based on furmonertinib’s preclinical activity observed against these mutations and the evaluation of furmonertinib in multiple clinical trials.
−Removed: Our Furmonertinib Development Initiative
−Removed: We have designed a robust global clinical development plan across a broad spectrum of EGFRm NSCLC patient populations for which we believe furmonertinib will have a differentiated profile compared to currently available treatments.
−Removed: The following table describes the key planned and ongoing clinical trials of furmonertinib conducted by us or our collaboration partners:
+Added: If approved, we believe firmonertinib has the potential to become a leading treatment option for first-line EGFRm NSCLC patients with PACC mutations based on firmonertinib’s preclinical and clinical activity observed against these mutations and the evaluation of firmonertinib in multiple clinical trials.
+Added: Our Firmonertinib Development Initiative
+Added: We have designed a robust global clinical development plan across a broad spectrum of EGFRm NSCLC patient populations for which we believe firmonertinib will have a differentiated profile compared to currently available treatments.
+Added: The following table describes the key planned and ongoing clinical trials of firmonertinib conducted by us or our collaboration partners:
Allist sponsor;
−Removed: ** Pursuant to InnoCare clinical collaboration agreement;
+Added: ** InnoCare sponsor;
First-Line Therapy;
Second-line or greater therapy;
−Removed: ^ Future planned cohort in 1L dependent on positive proof of concept in the 2L+ cohort.
FURVENT — Our Ongoing Phase 3 Clinical Trial in First-Line Non-Squamous Locally Advanced or Metastatic EGFRm NSCLC Patients with Exon 20 Insertion Mutations
−Removed: We are currently enrolling patients in FURVENT, a global, pivotal Phase 3 clinical trial of furmonertinib in first-line non-squamous locally advanced or metastatic NSCLC patients with exon 20 insertion mutations being conducted jointly with Allist.
−Removed: Our FURVENT clinical trial is designed to assess the safety and efficacy of furmonertinib administered at either 160 mg or 240 mg, once-daily as compared to platinum-based chemotherapy with pemetrexed, the current first-line standard of care.
+Added: We have enrolled our target of 375 patients in FURVENT, a global, pivotal Phase 3 clinical trial of firmonertinib in first-line non-squamous locally advanced or metastatic NSCLC patients with exon 20 insertion mutations being conducted jointly with Allist.
+Added: Our FURVENT clinical trial is designed to assess the safety and efficacy of firmonertinib administered at either 160 mg or 240 mg, once-daily as compared to platinum-based chemotherapy with pemetrexed, the current first-line standard of care.
The primary endpoint of this study is PFS.
−Removed: We plan to enroll 375 patients globally, including from sites in the United States, Europe and certain Asian countries including China.
+Added: We enrolled 375 patients globally, including from sites in the United States, Europe and certain Asian countries including China.
We expect topline data from our FURVENT clinical trial in 2025.
FURTHER — Our Ongoing Phase 1b Clinical Trial in NSCLC Patients with EGFR Activating Mutations including PACC Mutations
−Removed: We are currently enrolling patients in FURTHER, an ongoing, global Phase 1b dose escalation and expansion clinical trial being conducted jointly with Allist.
−Removed: It is intended to evaluate the safety, pharmacokinetics and preliminary anti-tumor activity as measured by confirmed complete response, defined as the disappearance of all target lesions, or partial response, defined as at least a 30% decrease in target lesions in the absence of a complete response, relative to the total number of patients, as a result of once-daily furmonertinib when used in patients with NSCLC involving locally advanced or metastatic disease that have previously received systemic therapy and whose tumors contain EGFR activating mutations.
−Removed: The pharmacokinetics, adverse events and serious adverse events experienced by patients and observed activity in the exon 20 patients of furmonertinib in the clinical trial to date are consistent with those observed in the FAVOUR clinical trial conducted in China.
−Removed: The FURTHER clinical trial includes a cohort of 60 patients diagnosed with a PACC EGFRm who are TKI treatment-naïve, which has been fully enrolled.
−Removed: We expect to announce clinical proof of concept data in EGFRm NSCLC patients with PACC mutations in 2024.
+Added: We have completed enrolling patients in FURTHER, an ongoing, global Phase 1b dose escalation and expansion clinical trial being conducted jointly with Allist.
+Added: It is intended to evaluate the safety, pharmacokinetics and preliminary anti-tumor activity of once-daily firmonertinib when used in patients with NSCLC involving locally advanced or metastatic disease that have previously received systemic therapy and whose tumors contain EGFR activating mutations.
+Added: Anti-tumor activity is measured by confirmed complete response, defined as the disappearance of all target lesions, or partial response, defined as at least a 30% decrease in target lesions in the absence of a complete response, relative to the total number of patients.
+Added: The pharmacokinetics, adverse events, serious adverse events, and observed anti-tumor activity in the exon 20 patients of firmonertinib in the clinical trial to date are consistent with those observed in the FAVOUR clinical trial conducted in China.
+Added: The FURTHER clinical trial includes a cohort of 60 patients with a PACC EGFRm who are TKI treatment-naïve, and has been fully enrolled.
+Added: In September 2024, we reported 64% of patients (n=14 out of 22 patients) treated at the 240 mg dose were observed to experience a confirmed reduction in tumor size of at least 30% from the baseline without evidence of progression as measured by RECIST 1.1 criteria .
FAVOUR — Ongoing Phase 1b Clinical Trial in NSCLC Patients with EGFR Exon 20 Insertion Mutations
−Removed: The FAVOUR clinical trial is an ongoing 90-patient Phase 1b clinical trial being conducted by Allist in China that is intended to assess the safety and efficacy of furmonertinib in locally advanced or metastatic NSCLC patients who have EGFR exon 20 insertion mutations.
−Removed: First-line patients receive 240 mg furmonertinib once daily.
−Removed: Patients that have received prior treatment are randomized to receive either 160 mg or 240 mg of furmonertinib once daily.
+Added: The FAVOUR clinical trial is an ongoing 90-patient Phase 1b clinical trial being conducted by Allist in China that is intended to assess the safety and efficacy of firmonertinib in locally advanced or metastatic NSCLC patients who have EGFR exon 20 insertion mutations.
+Added: First-line patients receive 240 mg firmonertinib once daily.
+Added: Patients that have received prior treatment are randomized to receive either 160 mg or 240 mg of firmonertinib once daily.
Initial data obtained through June 15, 2023 showed a confirmed ORR (defined as a reduction in tumor size of at least 30% from the baseline in a patient without evidence of progression), among patients evaluable as of that date of 79% among the treatment-naïve patients cohort, 46% among the pretreated 240 mg cohort and 39% in the pretreated 160 mg cohort.
−Removed: Median DOR was 15.2 months in treatment-naïve patients, 13.1 months in the 240 mg pretreated cohort and 9.7 months in the 160 mg pretreated patient cohort.
−Removed: Furmonertinib was observed to be generally well tolerated in all clinical trial cohorts to date with a low rate of discontinuation due to treatment-related adverse events (TRAEs).
+Added: Median DOR was 15.2 months in treatment-naïve patients, 13.1 months in the 240 mg pretreated cohort and 9.7 months in the 160 mg pretreated cohort.
+Added: Firmonertinib was observed to be generally well tolerated in all clinical trial cohorts to date with a low rate of discontinuation due to treatment-related adverse events (TRAEs).
As of June 15, 2023, treatment related serious adverse events (TRSAEs) were observed in 6 out of 86 of the treated patients and 2 out of 86 patients discontinued participation in the trial as a result of TRAEs.
−Removed: Allist expects to release final results of the primary analysis from the FAVOUR study in 2024.
SHP2 Combination Trial — Ongoing Phase 1b Clinical Trial in Classical EGFRm NSCLC Patients
−Removed: Given the eventual emergence of resistance that occurs with single agent EGFR TKIs we are also evaluating combination partner drugs with furmonertinib to treat or prevent resistance to third-generation EGFR TKIs.
−Removed: We are evaluating the use of furmonertinib in combination with ICP-189, a SHP2 (SHP2i), in collaboration with Beijing InnoCare Pharma Tech Co., Ltd.
−Removed: SHP2 is a protein tyrosine phosphatase that has an important role in the signaling pathways downstream of EGFR and other receptor tyrosine kinases (RTKs) that have been implicated in resistance such as the mesenchymal epithelial transition factor receptor (MET) tyrosine kinase.
+Added: Given the eventual emergence of resistance that occurs with EGFR TKIs we are also evaluating combination partner drugs with firmonertinib to treat or prevent resistance to third-generation EGFR TKIs.
+Added: We are evaluating the use of firmonertinib in combination with ICP-189, a SHP2 inhibitor (SHP2i), in collaboration with Beijing InnoCare Pharma Tech Co., Ltd.
+Added: SHP2 is a protein tyrosine phosphatase with an important role in the signaling pathways downstream of EGFR and other receptor tyrosine kinases (RTKs) that have been implicated in resistance such as the mesenchymal epithelial transition factor receptor (MET) tyrosine kinase.
We believe this therapeutic combination may not only further inhibit signaling pathways downstream from EGFR resulting in enhanced tumor shrinkage, but may also prevent the emergence of resistance due to signaling through other RTKs.
−Removed: We have submitted an Investigational New Drug Application (IND) to the NMPA’s Center for Drug Evaluation for a Phase 1b trial designed to evaluate the safety, pharmacokinetics and preliminary efficacy of the furmonertinib-ICP-189 combination in EGFRm NSCLC involving classical mutations and dosed the first patient in March 2024 for study in an expansion cohort in patients previously treated with a third-generation EGFR TKI with potential proof of concept in second-line classical EGFRm NSCLC in 2026, and 2027 in a planned EGFR-TKI naïve first-line therapy cohort.
−Removed: In addition, we are assessing the use of furmonertinib in combination with other novel agents as potential anti-cancer treatments with the intent to initiate additional combination studies in the future.
+Added: We have submitted an Investigational New Drug Application (IND) to the NMPA’s Center for Drug Evaluation for a Phase 1b trial designed to evaluate the safety, pharmacokinetics and preliminary efficacy of the firmonertinib-ICP- 189 combination in EGFRm NSCLC involving classical mutations and dosed the first patient in March 2024 and expect the potential proof of concept in second-line classical EGFRm NSCLC to become available in 2026.
Planned Adjuvant Study in NSCLC Patients with Uncommon EGFRm, including Exon 20 Insertion and PACC Mutations
The potential for EGFR TKIs that have demonstrated efficacy, safety and tolerability in the metastatic setting to improve disease-free and overall survival when administered in the adjuvant setting has been demonstrated by osimertinib in NSCLC patients with a classical EGFRm.
−Removed: We believe furmonertinib similarly has the potential to improve outcomes when administered as adjuvant therapy to EGFRm NSCLC patients with uncommon EGFRm, as these patients are not eligible for treatment with osimertinib.
−Removed: We intend to pursue an adjuvant study of furmonertinib in EGFRm NSCLC with uncommon mutations based on results obtained from currently ongoing clinical trials.
+Added: We believe firmonertinib similarly has the potential to improve outcomes when administered as adjuvant therapy to EGFRm NSCLC patients with uncommon EGFRm, as these patients are not eligible for treatment with osimertinib.
+Added: We intend to participate in a global adjuvant study of firmonertinib in EGFRm NSCLC with uncommon mutations initiated in China based on results obtained from currently ongoing clinical trials.
FURLONG — Completed Phase 3 Clinical Trial in Classical EGFRm First-Line NSCLC Patients
−Removed: FURLONG was a 358-patient clinical trial in China conducted by Allist, with results first reported in 2022, which resulted in the approval of furmonertinib in China as a first-line therapy in patients with locally advanced or metastatic NSCLC with classical EGFRm.
−Removed: It was designed to compare the safety and efficacy of once daily dosing of 80 mg furmonertinib to 250 mg gefitinib and supported the approval of furmonertinib in China as a first-line therapy in patients with locally advanced or metastatic NSCLC with classical EGFRm.
−Removed: Furmonertinib demonstrated clinically meaningful and statistically significant efficacy and a favorable safety profile as compared to the first-generation EGFR TKI gefitinib.
−Removed: Importantly, furmonertinib exhibited superior efficacy in the treatment of CNS metastases, producing a confirmed CNS metastases specific ORR, which measured reduction in tumor size of at least 30% in brain metastases if
−Removed: present at the start of therapy, of 91% versus 65% for gefitinib among participants with measurable metastatic CNS disease, demonstrating furmonertinib’s ability to cross the blood-brain barrier.
−Removed: Our Aarvik Antibody Drug Conjugate Collaboration
−Removed: Consistent with our focus on curating a pipeline of innovative, impactful oncology therapies across modalities, we are advancing next-generation antibody drug conjugates (ADCs).
+Added: FURLONG was a 358-patient clinical trial in China conducted by Allist, with results first reported in 2022, which resulted in the approval of firmonertinib in China as a first-line therapy in patients with locally advanced or metastatic NSCLC with classical EGFRm.
+Added: It was designed to compare the safety and efficacy of once daily dosing of 80 mg firmonertinib to 250 mg gefitinib.
+Added: Firmonertinib demonstrated clinically meaningful and statistically significant efficacy and a favorable safety profile as compared to the first-generation EGFR TKI gefitinib.
+Added: Importantly, firmonertinib exhibited superior efficacy in the treatment of CNS metastases, producing a confirmed CNS metastases specific ORR, which measured reduction in tumor size of at least 30% in brain metastases if present at the start of therapy, of 91% versus 65% for gefitinib among participants with measurable metastatic CNS disease, demonstrating firmonertinib’s ability to cross the blood-brain barrier.
+Added: Our Antibody Drug Conjugate Collaborations
+Added: Consistent with our focus on curating a pipeline of innovative, impactful oncology therapies across modalities, we are advancing next-generation ADCs.
ADCs are a promising modality for treating cancer due to their ability to target chemotherapy directly to the tumor cells.
−Removed: We are using Aarvik Therapeutics, Inc.’s (Aarvik) proprietary multi-target, multivalent site-specific conjugation antibody platform to discover and develop ADCs with improved activity and safety over single target bivalent ADCs.
−Removed: We anticipate identification of a lead candidate for IND enabling studies in late 2024 or early 2025.
+Added: We are using Aarvik’s proprietary multi-target, multivalent site-specific conjugation antibody platform to discover and develop ADCs with potentially improved activity and safety over single target bivalent ADCs.
+Added: We identified a preclinical candidate ARR-002 and have initiated IND-enabling activities.
+Added: We are also working with Alphamab to leverage their proprietary linker-payload platform and glycan-conjugation technology to discover, develop, and commercialize ADCs for the treatment of cancers.
+Added: Through our agreement with Lepu Biopharma, we are developing ARR-217, a novel ADC for the treatment of gastrointestinal cancers.
Our Team and Approach
−Removed: We were founded and acquired the rights to develop and commercialize furmonertinib worldwide, with the exception of greater China, which includes mainland China, Hong Kong, Macau and Taiwan, in 2021.
+Added: We were founded and acquired the rights to develop and commercialize firmonertinib worldwide, with the exception of greater China, which includes mainland China, Hong Kong, Macau and Taiwan, in 2021.
We believe that our deep expertise in developing oncology drugs, executing cross border business transactions and track record building companies will allow us to expand our portfolio globally, across the oncology landscape.
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Lutzker was Vice President and Head of Oncology, Early Clinical Development and oversaw the early clinical phase development of a number of approved products.
−Removed: We are also supported by a leading syndicate of investors, including Hillhouse, Lilly Asia Ventures, Octagon Capital, OrbiMed, Sirona Capital Partners and Sofinnova Investments.
See “Certain Relationships and Related Transactions, and Director Independence” for more information.
−Removed: Our team’s deep domain knowledge in oncology has allowed us to identify novel therapeutic programs with strong biologic and scientific rationale that we believe have the potential to offer a differentiated profile to treat cancer patients.
+Added: Our team’s deep knowledge in oncology has allowed us to identify novel therapeutic programs with strong biologic and scientific rationale that we believe have the potential to offer a differentiated profile to treat cancer patients.
Based on our extensive experience working with regulatory agencies, we will pursue assets that we believe have a clear regulatory path to approval.
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We believe that as the world’s second-largest pharmaceutical market, with extensive biopharmaceutical research and development capabilities, China provides us with attractive opportunities to in-license innovative therapies that otherwise may not reach global populations.
−Removed: We believe our business development acumen positions us to build a highly competitive pipeline that we are uniquely positioned to bring to global patient communities, beginning with our lead development asset, furmonertinib.
+Added: We believe our business development acumen positions us to build a highly competitive pipeline that we are uniquely positioned to bring to global patient communities, beginning with our lead development asset, firmonertinib.
We intend to become a leading biopharmaceutical company through the identification, development and commercialization of differentiated medicines to address the unmet medical needs of patients with cancers.
To accomplish this objective, we plan to:
−Removed: Maximize the potential of furmonertinib — develop and commercialize furmonertinib for the treatment of a broad array of EGFRm NSCLC indications.
−Removed: ● Advance furmonertinib through the pivotal Phase 3 FURVENT clinical trial and seek approval as a first-line therapy for non-squamous locally advanced or metastatic EGFRm NSCLC patients with exon 20 insertion mutations .
+Added: Maximize the potential of firmonertinib — develop and commercialize firmonertinib for the treatment of a broad array of EGFRm NSCLC indications.
+Added: ● Advance firmonertinib through the pivotal Phase 3 FURVENT clinical trial and seek approval as a first-line therapy for non-squamous locally advanced or metastatic EGFRm NSCLC patients with exon 20 insertion mutations .
Exon 20 insertion mutations represent one of the most prevalent uncommon EGFR mutations and make up over 9% of the EGFR NSCLC patient population.
−Removed: While the TKI mobocertinib and the bispecific antibody amivantamab have been approved as second-line therapy, no TKI has been approved as first-line therapy in this indication.
−Removed: We believe the interim data obtained as of June 15, 2023 in the Phase 1b FAVOUR clinical trial, in which patients were administered a 240 mg once-daily dose of furmonertinib, supports the progression of furmonertinib to the next phase of clinical trials.
−Removed: In that interim data readout, 79% of patients (n=22 out of 28 patients) were observed to experience a reduction in tumor size of at least 30% from the baseline in a patient without evidence of progression as measured by RECIST 1.1 criteria, which measurement of reduction is the threshold in this trial for a partial response and for inclusion in determination of the ORR, which is the primary endpoint of this trial.
−Removed: We received Breakthrough Therapy Designation for furmonertinib for the treatment of this disease from the FDA in October 2023, and Orphan Drug Designation for treatment of NSCLC with EGFRm or HER2 mutations or HER4 mutations in February 2024 .
+Added: While the antibody amivantamab has been approved as second-line therapy and chemotherapy in combination with amivantamab approved in first line therapy, no TKI has been approved as first-line therapy in this indication.
+Added: We believe the interim data obtained as of June 15, 2023 in the Phase 1b FAVOUR clinical trial, in which patients were administered a 240 mg once-daily dose of firmonertinib, supports the progression of firmonertinib to the next phase of clinical trials.
+Added: In that interim data readout, 79% of treatment naïve patients (n=22 out of 28 patients) were observed to experience a reduction in tumor size of at least 30% from the baseline in a patient without evidence of progression as measured by RECIST 1.1 criteria.
+Added: This measurement of reduction is the threshold in this trial for a partial response and for inclusion in determination of the ORR, which is the primary endpoint of this trial.
+Added: We received Breakthrough Therapy Designation for firmonertinib for the treatment of this disease from the FDA in October 2023, and Orphan Drug Designation for treatment of NSCLC with EGFRm or HER2 mutations or HER4 mutations in February 2024 .
We do not currently intend to conduct a Phase 2 trial in first-line non-squamous locally advanced or metastatic EGFRm NSCLC patients with exon 20 insertion mutations.
−Removed: Accordingly, we are currently enrolling patients in our global, pivotal Phase 3 FURVENT clinical trial in first-line non-squamous locally advanced or metastatic EGFRm NSCLC patients with exon 20 insertion mutations and we expect topline data from this clinical trial in 2025.
−Removed: ● Continue to advance furmonertinib through the Phase 1b FURTHER clinical trial in EGFRm NSCLC to obtain proof of concept for the treatment of patients with PACC mutations.
−Removed: We are also advancing the clinical development of furmonertinib as a potential treatment for EGFRm NSCLC patients with PACC mutations.
+Added: We have completed enrollment in our global, pivotal Phase 3 FURVENT clinical trial in first-line non-squamous locally advanced or metastatic EGFRm NSCLC patients with exon 20 insertion mutations and we expect topline data from this clinical trial in 2025.
+Added: ● Continue to advance firmonertinib through the Phase 1b FURTHER clinical trial in EGFRm NSCLC to obtain proof of concept for the treatment of patients with PACC mutations.
+Added: We are also advancing the clinical development of firmonertinib as a potential treatment for EGFRm NSCLC patients with PACC mutations.
PACC mutations are a distinct set of approximately 70 EGFR-activating mutations, associated with over 12% of EGFRm NSCLC patients.
Guidelines employing TKIs for many of the PACC-specific EGFR mutations are not established and, as a result, chemotherapy is often used as the default course of therapy, offering limited efficacy and introducing chemotherapy-related toxicity.
+Added: Osimertinib is frequently used in some patients, but the activity of osimertinib is much less than in classical EGFR mutant NSCLC.
Afatinib, a second-generation TKI, is also used in some patients, but has a poor safety profile and is not brain penetrant.
−Removed: We are investigating the use of furmonertinib to treat a broad set of PACC mutations in a cohort in our FURTHER clinical trial based on furmonertinib’s observed activity against PACC mutations in preclinical studies together with the evaluation of furmonertinib in multiple clinical trials with an aggregate patient population of over 700 patients.
+Added: We are investigating the use of firmonertinib to treat a broad set of PACC mutations in a cohort in our FURTHER clinical trial based on firmonertinib’s observed activity against PACC mutations in preclinical studies together with the evaluation of firmonertinib in multiple clinical trials with an aggregate patient population of over 1000 patients, including over 450 patients outside China.
Other cohorts in the FURTHER trial include patients with EGFR exon 20 insertion mutations as second-line or greater therapy.
−Removed: ● Evaluate the clinical benefit of treating early-stage disease with furmonertinib.
−Removed: We also intend to initiate a global registrational Phase 3 clinical trial to investigate the potential benefit of furmonertinib in the adjuvant setting in NSCLC patients with uncommon EGFRm that are not eligible for osimertinib such as exon 20 insertion and PACC mutations.
−Removed: We intend to pursue an adjuvant study of furmonertinib once the EGFRm patient group is further defined based on ongoing clinical trials in the metastatic setting.
−Removed: We have not yet sought alignment on the design of our planned adjuvant study with the FDA or comparable foreign regulatory authorities.
−Removed: Such authorities may ask us to collect more clinical data prior to permitting us to initiate the planned global registrational Phase 3 clinical trial to investigate the potential benefit of furmonertinib in the adjuvant setting.
−Removed: ● Employ combination strategies with furmonertinib to overcome and prevent resistance to EGFR TKI in NSCLC involving classical mutations.
+Added: ● Evaluate the clinical benefit of treating early-stage disease with firmonertinib.
+Added: We also intend to participate in a global registrational Phase 3 clinical trial initiated in China to investigate the potential benefit of firmonertinib in the adjuvant setting in NSCLC patients with uncommon EGFRm that are not eligible for osimertinib such as exon 20 insertion and PACC mutations.
+Added: We intend to join the adjuvant study of firmonertinib once the EGFRm patient group is further defined based on ongoing clinical trials in the metastatic setting.
+Added: We have not yet sought alignment on the design of the adjuvant study with the FDA who may ask us to collect more clinical data prior to joining the adjuvant study.
+Added: ● Employ combination strategies with firmonertinib to overcome and prevent resistance to EGFR TKI in NSCLC involving classical mutations.
Acquired resistance presents an inevitable challenge to longer-term EGFRm NSCLC management.
−Removed: As such, we are evaluating the use of furmonertinib in combination with other signal transduction inhibitors which we believe have the potential to both treat and prevent acquired resistance.
−Removed: initial combination strategy involves the evaluation of furmonertinib together with a SHP2 inhibitor for use in treating NSCLC patients involving classical EGFRm that have progressed on prior EGFR TKI and we have initiated a Phase 1b clinical trial designed to evaluate the safety, pharmacokinetics and preliminary efficacy of the combination with clinical proof of concept data expected in 2026 in a second-line therapy cohort, and in 2027 in a planned EGFR-TKI naïve first-line therapy cohort.
+Added: As such, we are evaluating the use of firmonertinib in combination with a signal
+Added: transduction inhibitor which we believe has the potential to both treat and prevent acquired resistance.
+Added: Our initial combination strategy involves the evaluation of firmonertinib together with a SHP2 inhibitor for use in treating NSCLC patients involving classical EGFRm that have progressed on prior EGFR TKI therapy and we have initiated a Phase 1b clinical trial designed to evaluate the safety, pharmacokinetics and preliminary efficacy of the combination with clinical proof of concept data expected in 2026 in a second-line therapy cohort.
Advance novel therapeutic product candidates for unmet medical needs, leveraging innovative platforms and technologies starting with ADCs.
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ADCs are a promising modality for treating cancer due to their ability to target chemotherapy directly to the tumor cells.
−Removed: We have entered into a research collaboration with Aarvik to leverage its proprietary multi-target, multivalent, site-specific conjugation antibody platform to discover ADCs with improved activity and safety over single target bivalent ADCs.
−Removed: We anticipate identification of a lead candidate for IND-enabling studies in late 2024 or early 2025.
+Added: We have entered into a research collaboration with Aarvik to leverage its proprietary multi-target, multivalent, site-specific conjugation antibody platform to discover ADCs with potentially improved activity and safety over single target bivalent ADCs.
+Added: We identified a preclinical candidate, ARR-002, and have initiated IND-enabling activities.
+Added: We have also entered into a collaboration with Alphamab to discover, develop and commercialize novel ADCs.
+Added: We are working with Alphamab to leverage their proprietary linker-payload platform and glycan-conjugation technology to identify novel ADCs for oncology indications globally, except greater China, which includes mainland China, Hong Kong, Macau and Taiwan where Alphamab retains the right to develop and commercialize ADCs.
+Added: We entered into a license agreement with Lepu Biopharma pursuant to which Lepu Biopharma granted us a right to develop and commercialize ARR-217, an antibody drug conjugate for gastrointestinal cancers outside greater China, which is mainland China, Hong Kong, Macau and Taiwan.
Broaden our pipeline through expanded business development initiatives.
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We intend to use our demonstrated capabilities in business development to establish additional collaborations and acquire the rights to drug candidates designed to treat solid tumors and address significant unmet medical needs of patients with cancers.
−Removed: While we source candidates from across the globe, our initial focus has been on drugs originally discovered and developed in China for potential commercialization in the United States and the European Union.
+Added: While we source candidates from across the globe, our initial focus has been on drugs originally discovered and developed in China for potential commercialization in the United States, the European Union, and other jurisdictions.
For programs that we in-license, we plan to pursue a global development strategy to enable approval and commercialization in a broad set of geographies.
We remain agnostic as to therapeutic modality, which we believe will expand our access to drug candidates with attractive therapeutic profiles.
+Added: In January 2025, we entered into an exclusive license agreement with Lepu Biopharma, pursuant to which Lepu Biopharma granted us a right to develop and commercialize ARR-217, an antibody drug conjugate for gastrointestinal cancers outside greater China, which is mainland China, Hong Kong, Macau and Taiwan.
+Added: ● Track record of establishing collaborations and license agreements.
+Added: Since our inception in 2021, we have established two licensing agreements for oncology assets, two ADC collaborations and a clinical collaboration.
+Added: We believe in continuing to build our pipeline through sourcing innovation globally and remaining nimble in developing such programs in collaboration with our partners.
According to the National Cancer Institute, lung cancer is predicted to account for nearly 250,000 of the two million new cancer diagnoses made in the United States in 2023.
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EGFRm are detected by numerous commercially available FDA-approved DNA tests, either PCR or NGS, utilizing either tumor tissue or blood samples and testing for EGFRm, as well as other activating gene mutations, is considered standard in the management of NSCLC as per national guidelines such as NCCN.
−Removed: We are working with a diagnostics company to develop an FDA-approved NGS test for confirming EGFR exon 20 insertion mutations in our clinical trial and if furmonertinib is approved, we believe it would be indicated for patients with EGFRm as detected by an FDA-approved DNA test.
+Added: We are working with a diagnostics company to develop an FDA-approved NGS test for confirming EGFR exon 20 insertion mutations in our clinical trial and if firmonertinib is approved, we believe it would be indicated for patients with EGFRm as detected by an FDA-approved DNA test.
EGFR activating mutations include both classical and uncommon mutations in the kinase domain
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However, TRAEs are more pronounced than the first-generation designs, which have limited broader clinical application of the second-generation TKIs.
−Removed: Osimertinib was the first third-generation TKI to receive FDA approval and is currently the standard of care for patients with EGFRm NSCLC involving classical mutations and the related treatment emergent T790M mutation in the majority of countries worldwide.
+Added: Osimertinib was the first third-generation TKI to receive FDA approval and is currently a standard of care for patients with EGFRm NSCLC involving classical mutations and the related treatment emergent T790M mutation in the majority of countries worldwide.
Osimertinib provides an improved AE profile, including a reduction in severe adverse events, compared to the earlier generation EGFR targeted TKIs and displays a greater ability to cross the blood-brain barrier, enabling efficacy against metastases involving the CNS.
The ability to treat CNS metastases is of notable importance as patients with EGFR-activating mutations are particularly susceptible to the development of brain metastases, which can occur in up to 70% of patients during the course of their disease.
+Added: In 2024, amivantamab in combination with lazertinib was approved for the treatment of first-line NSCLC patients with EGFR Exon 19 deletions or Exon 21 L858R substitution mutations.
+Added: Amivantamab is a bispecific antibody and lazertinib is a third-generation
The key limitations of the current standard of care for patients with EGFRm NSCLC involving classical mutations is presented in the graphic below:
Table includes approved and disclosed registrational indications
−Removed: Afatinib has Iimited clinical data in patients with 2 of the 70 described PACC mutations
−Removed: PAPILLON study in 1L announced as positive
−Removed: Exclaim-2 study in 1L announced as negative and in October 2023, Takeda announced it is working with the FDA towards a voluntary withdrawal of mobocertinib in the United States and intends to similarly initiate voluntary withdrawal globally for patients with EGFR exon 20 insertion mutation-positive locally advanced or metastatic NSCLC whose disease has progressed on or after platinum-based chemotherapy.
+Added: *Afatinib has limited clinical data in patients with 2 of the 70 described PACC mutations.
+Added: **Exclaim-2 study in 1L announced as negative and in July 2024, the FDA withdrew the license for mobocertinib in the United States
+Added: Dacomitinib is also approved in the United States for classical EGFR mutations
There is currently no TKI approved as first-line therapy for NSCLC patients with EGFR exon 20 insertion mutations.
−Removed: Platinum-based chemotherapy with pemetrexed remains the standard of care for first-line therapy in this patient population in the United States and the European Union.
+Added: Platinum-based chemotherapy with pemetrexed is a standard of care for first-line therapy in this patient population in the United States and the European Union with or without amivantamab.
Of particular note, approximately one-third of NSCLC patients harboring EGFR exon 20 insertion mutations have brain metastases at the time of diagnosis, which are mainly treated with radiation therapy, as chemotherapy is less effective in the treatment of brain metastases due to low brain penetration.
−Removed: In 2021, the FDA granted marketing approval to two therapeutics, mobocertinib, a TKI and amivantamab, a bispecific antibody, used to treat NSCLC patients with exon 20 insertion mutations which have progressed after administration of platinum-based chemotherapy.
+Added: In 2021, the FDA granted marketing approval to two therapeutics, mobocertinib, a TKI, and amivantamab, a bispecific antibody, to treat NSCLC patients with exon 20 insertion mutations which have progressed after administration of platinum-based chemotherapy.
Both approvals were granted under accelerated approval and continued approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
−Removed: Notably, in July 2023, Takeda announced the discontinuation of its Phase 3 clinical trial of mobocertinib as a monotherapy in first-line patients due to futility, which may impact its continued approval.
+Added: Notably, in July 2023, Takeda announced the discontinuation of its Phase 3 clinical trial of mobocertinib as a monotherapy in first-line patients due to futility and subsequently withdrew the drug from the market globally.
In August 2023, Johnson & Johnson announced that its Phase 3 trial of amivantamab in combination with chemotherapy in first-line patients met its primary endpoint of PFS when compared to chemotherapy alone.
−Removed: While the FDA approved the use of this combination in this patient population in March 2024, the use of amivantamab in the first-line patients may be limited due to the need to combine with intravenous chemotherapy.
+Added: While the FDA approved the use of this combination in this patient population in March 2024, and by the European Commission in July 2024, the use of chemotherapy in combination with amivantamab in the first-line patients may be limited due to the need to combine with intravenous chemotherapy and lack of brain penetration of amivantamab, along with chemotherapy associated toxicities.
A distinct set of approximately 70 uncommon EGFR-activating mutations have been identified that are predicted to alter the orientation of the interior surface of the ATP-binding pocket of the EGFR P-loop or αC-terminal end of the C-helix within the tyrosine kinase domain and are referred to as PACC mutations.
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Guidelines employing TKIs for many of the PACC-specific EGFRm are not established and as a result chemotherapy is used as the default course of therapy in many patients with limited clinical benefit.
−Removed: The second-generation TKI afatinib is the only TKI to have received FDA and the European Medical Association approval in NSCLC to treat EGFRm NSCLC with limited clinical data for two of the 70 PACC mutations, G719X and S768I.
−Removed: The current treatment paradigm for the various subtypes of EGFRm NSCLC outside of China and areas of unmet medical needs where we believe furmonertinib may provide clinical utility is summarized in the chart presented below.
−Removed: Furmonertinib has the potential to address significant unmet needs in the current EGFRm NSCLC treatment paradigm
+Added: Osimertinib is frequently used in some patients, but the activity of osimertinib is much less than in classical EGFRm NSCLC.
+Added: The second-generation TKI
+Added: afatinib is the only TKI to have received FDA and the European Medical Association approval in NSCLC to treat EGFRm NSCLC with limited clinical data for two of the 70 PACC mutations, G719X and S768I.
+Added: The current treatment paradigm for the various subtypes of EGFRm NSCLC outside of China and areas of unmet medical needs where we believe firmonertinib may provide clinical utility is summarized in the chart presented below.
+Added: Firmonertinib has the potential to address significant unmet needs in the current EGFRm NSCLC treatment paradigm
Specific to the HER2 exon 20 insertion mutation, an exon 20 insertion in the related HER2 gene, in August 2022 the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (ENHERTU ® ), a HER2-directed antibody-drug conjugate, for adults with unresectable or metastatic NSCLC who have received prior systemic therapy.
Despite its approval, patients with refractory or recurrent disease remain a significant portion of the patient population and currently approved TKIs have demonstrated limited efficacy in targeted HER2 exon 20 insertion mutations.
−Removed: Furmonertinib:
+Added: Firmonertinib:
Our Lead Development Candidate
−Removed: Our lead development candidate is furmonertinib, an investigational, novel, EGFR mutant-selective TKI that we are developing for the treatment of patients with NSCLC harboring a broader set of EGFRm than are currently served by approved EGFR TKIs.
−Removed: Furmonertinib is currently approved and commercially distributed by Allist in China as a first-line treatment of locally advanced or metastatic NSCLC patients with classical EGFRm as well as pre-treated patients with T790M mutations.
−Removed: In addition, in an interim data readout from the FAVOUR trial of furmonertinib, reductions in tumor size have been observed in patients with exon 20 insertion mutations and activity in PACC mutations has been observed in a preclinical setting.
+Added: Our lead development candidate is firmonertinib, an investigational, novel, EGFR mutant-selective TKI that we are developing for the treatment of patients with NSCLC harboring a broader set of EGFRm than are currently served by approved EGFR TKIs.
+Added: Firmonertinib is currently approved and commercially distributed by Allist in China as a first-line treatment of locally advanced or metastatic NSCLC patients with classical EGFRm as well as pre-treated patients with T790M mutations.
+Added: In addition, in an interim data readout from the FAVOUR trial of firmonertinib, reductions in tumor size have been observed in patients with exon 20 insertion mutations and activity in PACC mutations has been observed in an interm data readout from the FURTHER trial.
Exon 20 insertion mutations and PACC mutations are each a subtype of uncommon mutation.
Exon 20 insertions and PACC mutations account for approximately 22% of EGFRm NSCLC patients and are largely underserved by existing treatments.
−Removed: Furmonertinib has been studied in over 700 patients, including over 70 patients outside China, across a broad dose range.
−Removed: We anticipate that favorable safety data, if obtained for furmonertinib, could allow for the administration of furmonertinib at different doses required for optimal activity in different EGFRm patient populations.
−Removed: Encouraging activity has been observed to date in both preclinical and clinical settings, including response in CNS metastases, in an interim data readout from our partner’s ongoing FAVOUR clinical trial in China with patients with exon 20 insertions, and in preclinical activity against PACC mutations.
−Removed: Of particular note, furmonertinib exhibited elevated tissue distribution to the brain in preclinical studies.
−Removed: In these studies, the brain and plasma concentrations were measured in mice following a single dose of either furmonertinib or osimertinib and the brain-to-plasma calculated for both total drug (Kp) and unbound drug (Kp uu).
+Added: Firmonertinib has been studied in over 1000 patients, including over 450 patients outside China, across a broad dose range.
+Added: We anticipate that favorable safety data, if obtained for firmonertinib, could allow for the administration of firmonertinib at different doses required for optimal activity in different EGFRm patient populations.
+Added: Encouraging activity has been observed to date in both preclinical and clinical settings, including response in CNS metastases, in an interim data readout from our partner’s ongoing FAVOUR clinical trial in China with patients with exon 20 insertions, and in the ongoing FURTHER clinical trial in patients with PACC mutations globally.
+Added: Of particular note, firmonertinib exhibited elevated tissue distribution to the brain in preclinical studies.
+Added: In these studies, the brain and plasma concentrations were measured in mice following a single dose of either firmonertinib or
+Added: osimertinib and the brain-to-plasma calculated for both total drug (Kp) and unbound drug (Kp uu).
Osimertinib was used as a reference compound in certain experiments as it has demonstrated clinical activity in patients with CNS metastases.
−Removed: As is noted in the chart below, these experiments showed that furmonertinib penetrated the blood-brain barrier at a rate similar to that of osimertinib.
−Removed: Furmonertinib displayed brain penetrant properties similar to osimertinib in pre-clinical studies.
−Removed: When mice were administered a single dose of either furmonertinib or osimertinib, they penetrated the blood-brain barrier to a similar extent.
−Removed: We are currently conducting our FURVENT clinical trial, a global, pivotal Phase 3 clinical trial of furmonertinib in first-line non-squamous locally advanced or metastatic NSCLC patients with exon 20 insertion mutations and we expect topline data in 2025.
−Removed: In addition, we are conducting our FURTHER trial, a Phase 1b dose escalation and expansion clinical trial in patients with EGFRm NSCLC, including a cohort with PACC mutations which has been fully enrolled, and we expect proof of concept data from this cohort in 2024.
−Removed: Subject to review of data and regulatory feedback, we intend to expand this Phase 1b clinical trial into a potentially registrational clinical trial for NSCLC patients with PACC mutations.
+Added: As is noted in the chart below, these experiments showed that firmonertinib penetrated the blood-brain barrier at a rate similar to that of osimertinib.
+Added: Firmonertinib displayed brain penetrant properties similar to osimertinib in pre-clinical studies.
+Added: When mice were administered a single dose of either firmonertinib or osimertinib, they penetrated the blood-brain barrier to a similar extent.
+Added: We are currently conducting our FURVENT clinical trial, a global, pivotal Phase 3 clinical trial of firmonertinib in first-line non-squamous locally advanced or metastatic NSCLC patients with exon 20 insertion mutations and we expect topline data in 2025.
+Added: In addition, we are conducting our FURTHER trial, a Phase 1b dose escalation and expansion clinical trial in patients with EGFRm NSCLC, including a cohort with PACC mutations which has been fully enrolled, and we presented proof of concept data from this cohort in September 2024.
+Added: Subject to review of data and regulatory feedback, we intend to initiate a registrational clinical trial for NSCLC patients with PACC mutations.
Data from our partner’s completed and ongoing clinical trials and from our ongoing clinical trials are discussed below.
FURVENT — Our ongoing Phase 3 Clinical Trial in First-Line Non-Squamous Locally Advanced or Metastatic EGFRm NSCLC Patients with Exon 20 Insertion Mutations
−Removed: We are currently enrolling patients in FURVENT, a global, pivotal Phase 3 clinical trial of furmonertinib in first-line non-squamous locally advanced or metastatic EGFRm NSCLC patients with exon 20 insertion mutations being conducted jointly with Allist.
−Removed: We designed a randomized clinical trial, integrating feedback from global regulatory agencies, that consists of three cohorts of 125 patients each, designed to evaluate the safety and efficacy of furmonertinib at two different dose levels, 160 mg and 240 mg, administered daily (QD) and compare therapeutic benefit to platinum-based chemotherapy cycles with pemetrexed, the clinical trial’s active control group.
−Removed: Participants in this clinical trial will continue to receive treatment until disease progression or discontinuation related to toxicity, with patients in the control group allowed to cross over into one of the two furmonertinib arms after disease progression.
−Removed: The primary endpoint of this trial is PFS per blinded independent central review utilizing Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
+Added: We have completed enrolling patients in FURVENT, a global, pivotal Phase 3 clinical trial of firmonertinib in first-line non-squamous locally advanced or metastatic EGFRm NSCLC patients with exon 20 insertion mutations being conducted jointly with Allist.
+Added: We designed a randomized clinical trial, integrating feedback from global regulatory agencies, that consists of three cohorts of 125 patients each, designed to evaluate the safety and efficacy of firmonertinib at two different dose levels, 160 mg and 240 mg, administered daily (QD) and compare therapeutic benefit to platinum-based chemotherapy cycles with pemetrexed, the clinical trial’s active control group.
+Added: Participants in this clinical trial will continue to receive treatment until disease progression or discontinuation related to toxicity, with patients in the control group allowed to cross over into one of the two firmonertinib arms after disease progression.
+Added: The primary endpoint of this trial is PFS per blinded independent central review utilizing RECIST 1.1 criteria.
Secondary endpoints include ORR, overall survival (OS) and DOR, as well as brain-specific ORR and PFS in patients with brain metastases.
−Removed: We are currently enrolling patients in this clinical trial and anticipate top-line data for the use of furmonertinib as first-line therapy in patients with non-squamous locally advanced or metastatic EGFRm NSCLC with exon 20 insertion mutations in 2025.
+Added: We are currently enrolling patients in this clinical trial and anticipate top-line data for the use of firmonertinib as first-line
+Added: therapy in patients with non-squamous locally advanced or metastatic EGFRm NSCLC with exon 20 insertion mutations in 2025.
The FURVENT clinical trial’s study design is illustrated below:
FURTHER — Our Ongoing Phase 1b Clinical Trial in NSCLC Patients with EGFR Activating Mutations including PACC Mutations
−Removed: We are currently enrolling patients in FURTHER, an ongoing, global Phase 1b dose escalation and expansion clinical trial being conducted jointly with Allist.
−Removed: It is intended to evaluate the safety, pharmacokinetics and reduction in tumor size as a result of once-daily furmonertinib when used in locally advanced or metastatic non-squamous EGFRm NSCLC patients that have previously received systemic therapy and whose tumors contain EGFR activating mutations, including both classical and uncommon, as well as HER2 exon 20 insertion mutations.
+Added: We completed enrolling patients in FURTHER, an ongoing, global Phase 1b dose escalation and expansion clinical trial being conducted jointly with Allist.
+Added: It is intended to evaluate the safety, pharmacokinetics and reduction in tumor size as a result of once-daily firmonertinib when used in locally advanced or metastatic non-squamous EGFRm NSCLC patients that have previously received systemic therapy and whose tumors contain EGFR activating mutations, including both classical and uncommon, as well as HER2 exon 20 insertion mutations.
Cohort 4 specifically enrolls patients with EGFR PACC mutations.
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Currently, afatinib, a second-generation EGFR TKI has data supporting its use in two of the approximately 70 PACC mutations (S768I and G719X).
−Removed: Our preclinical data to date suggest that furmonertinib may have activity against a significantly broader number of PACC mutations.
−Removed: In seeking to enroll patients for this trial, we are engaging with medical oncology centers around the globe with experience identifying and enrolling EGFRm patients on clinical trials.
−Removed: The first stage of the FURTHER clinical trial enrolled a
−Removed: broad group of EGFRm NSCLC patients to evaluate pharmacokinetics and safety in patients outside of China and identify a dose for the expansion cohorts shown below.
+Added: Our preclinical data to date suggest that firmonertinib may have activity against a significantly broader number of PACC mutations.
+Added: first stage of the FURTHER clinical trial enrolled a broad group of EGFRm NSCLC patients to evaluate pharmacokinetics and safety in patients outside of China and identify a dose for the expansion cohorts shown below.
● Cohort One is designed to enroll 20 patients with locally advanced or metastatic EGFR exon 20 insertion positive NSCLC who have previously received systemic treatment and may have received prior EGFRm targeting TKI therapeutic or amivantamab.
−Removed: Patients in Cohort One are to receive 240 mg furmonertinib once daily.
+Added: Patients in Cohort One are to receive 240 mg firmonertinib once daily.
● Cohort Two is designed to enroll 20 patients with locally advanced or metastatic HER2 exon 20 insertion positive NSCLC, a mutation and patient population that is distinct from the exon 20 mutation and patient population.
−Removed: Patients in Cohort Two will have previously received systemic treatment and are to receive 240 mg furmonertinib once daily.
+Added: Patients in Cohort Two will have previously received systemic treatment and are to receive 240 mg firmonertinib once daily.
● Cohort Three is designed to enroll 20 patients with locally advanced or metastatic NSCLC with an EGFR-activating mutation other than exon 20 insertion or PACC mutations who have previously received systemic treatment.
Patients with classical EGFRm must have received prior osimertinib therapy.
−Removed: Participants in Cohort Three are to receive 240 mg furmonertinib once daily.
+Added: Participants in Cohort Three are to receive 240 mg firmonertinib once daily.
● Cohort Four is designed to enroll 60 patients with locally advanced or metastatic NSCLC with EGFR PACC mutations who are TKI-treatment naive.
−Removed: Patients in Cohort Four are randomized into two groups, one group of up to 30 patients to receive 160 mg furmonertinib once-daily and the other group of up to 30 patients administered 240 mg furmonertinib once-daily.
−Removed: Pharmacokinetic data obtained in the first stage of the FURTHER clinical trial as of June 15, 2023 were consistent with initial pharmacokinetic data obtained in the FAVOUR clinical trial as of June 15, 2023 with similar steady-state levels of furmonertinib and its major metabolite, AST5902 (see figure below).
+Added: Patients in Cohort Four are randomized into two groups, one group of up to 30 patients to receive 160 mg firmonertinib once-daily and the other group of up to 30 patients administered 240 mg firmonertinib once-daily.
+Added: Pharmacokinetic data obtained in the first stage of the FURTHER clinical trial as of June 15, 2023 were consistent with initial pharmacokinetic data obtained in the FAVOUR clinical trial as of June 15, 2023 with similar steady-state levels of firmonertinib and its major metabolite, AST5902 (see figure below).
The AEs in the FURTHER clinical trial have been consistent with the EGFR targeted TKI class in general, with diarrhea, stomatitis and rash being the most commonly observed TRAEs.
The frequency of dose reduction and discontinuation due to AEs has remained low.
−Removed: evidence of reduction in tumor size has been observed, with confirmed and unconfirmed partial responses to furmonertinib noted in NSCLC patients with mutations involving EGFR exon 20 insertions.
−Removed: Furmonertinib has shown similar drug levels at steady state in both the FAVOUR and the FURTHER clinical trials
−Removed: Reduction in tumor size observed in preclinical studies with furmonertinib in uncommon EGFR mutations
−Removed: We advanced furmonertinib into clinical trials as a potential treatment for EGFR mutation-positive NSCLC involving uncommon mutations based on compelling data demonstrating reduction in tumor size in preclinical studies using mouse xenografts, as presented below.
−Removed: As is detailed in the illustration presented below, in this LU0387 patient derived tumor xenograft model with an EGFR exon 20 insertion mutation H773_V774insNPH, once daily oral dosing of furmonertinib at 20 mg/kg, 30 mg/kg or 50 mg/kg, which equates to an approximate human dose of 40 mg, 160 mg or 240 mg respectively, was observed to induce significant tumor growth inhibition with regression of tumors at the 50 mg/kg dose with minimum change to bodyweight.
−Removed: Furmonertinib displayed reduction in tumor size in EGFR exon 20 insertion mutations tumor model
+Added: evidence of reduction in tumor size has been observed, with confirmed and unconfirmed partial responses to firmonertinib noted in NSCLC patients with mutations involving EGFR exon 20 insertions.
+Added: Firmonertinib has shown similar drug levels at steady state in both the FAVOUR and the FURTHER clinical trials
+Added: Reduction in tumor size observed in preclinical studies with firmonertinib in uncommon EGFR mutations
+Added: We advanced firmonertinib into clinical trials as a potential treatment for EGFR mutation-positive NSCLC involving uncommon mutations based on compelling data demonstrating reduction in tumor size in preclinical studies using mouse xenografts, as presented below.
+Added: As is detailed in the illustration presented below, in this LU0387 patient derived tumor xenograft model with an EGFR exon 20 insertion mutation H773_V774insNPH, once daily oral dosing of firmonertinib at 20 mg/kg, 30 mg/kg or 50 mg/kg, which equates to an approximate human dose of 40 mg, 160 mg or 240 mg respectively, was observed to induce significant tumor growth inhibition with regression of tumors at the 50 mg/kg dose with minimum change to bodyweight.
+Added: Firmonertinib displayed reduction in tumor size in EGFR exon 20 insertion mutations tumor model
Similar reduction in tumor size was observed in a Ba/F3 subcutaneous tumor xenograft model harboring a G724S PACC mutation as shown below.
−Removed: This PACC mutation is less sensitive to furmonertinib than other PACC mutations based on cell line data.
−Removed: The oral administration of 15 mg/kg, 30 mg/kg or 50 mg/kg furmonertinib one time per day produced pronounced significant inhibition of tumor growth with regression of tumors at the two higher doses.
+Added: This PACC mutation is less sensitive to firmonertinib than other PACC mutations based on cell line data.
+Added: The oral administration of 15 mg/kg, 30 mg/kg or 50 mg/kg firmonertinib one time per day produced pronounced significant inhibition of tumor growth with regression of tumors at the two higher doses.
We believe the limited loss of body weight suggests that the drug was generally well tolerated.
−Removed: Tumor growth inhibition was observed in an EGFR G724S PACC mutation tumor model with furmonertinib
−Removed: The in vivo efficacy of furmonertinib was also evaluated in a subcutaneous Ba/F3 tumor xenograft model with a HER2 exon 20 insertion mutation V777_G778insGC as illustrated below.
−Removed: B-NDG mice administered an oral dose of 15 mg/kg, 30 mg/kg or 50 mg/kg furmonertinib once daily were observed to exhibit significant tumor growth inhibition with regression at the two higher doses.
−Removed: Moreover, furmonertinib appeared generally well tolerated with minimal change in body weight.
−Removed: Reduction in tumor size was observed in a HER2 exon 20 insertion mutation tumor model with furmonertinib
+Added: Tumor growth inhibition was observed in an EGFR G724S PACC mutation tumor model with firmonertinib
+Added: The in vivo efficacy of firmonertinib was also evaluated in a subcutaneous Ba/F3 tumor xenograft model with a HER2 exon 20 insertion mutation V777_G778insGC as illustrated below.
+Added: B-NDG mice administered an oral dose of 15 mg/kg, 30 mg/kg or 50 mg/kg firmonertinib once daily were observed to exhibit significant tumor growth inhibition with regression at the two higher doses.
+Added: Moreover, firmonertinib appeared generally well tolerated with minimal change in body weight.
+Added: Reduction in tumor size was observed in a HER2 exon 20 insertion mutation tumor model with firmonertinib
+Added: FURTHER Cohort 4 — Our Ongoing Phase 1b Clinical Trial in NSCLC Patients with EGFR Activating PACC Mutations
+Added: The FURTHER clinical trial cohort 4 enrolled 60 patients with locally advanced or metastatic NSCLC with EGFR PACC mutations who are TKI-treatment naive.
+Added: Patients in Cohort 4 are randomized into two groups, one group of up to 30 patients to receive 160 mg firmonertinib once-daily and the other group of up to 30 patients administered 240 mg firmonertinib once-daily.
+Added: Patients with asymptomatic metastases involving the CNS are allowed to participate in the trial.
+Added: The primary endpoint of this trial is ORR as measured by the Response Evaluation Criteria In Solid Tumors (version 1.1) by Blinded Independent Central Review.
+Added: Secondary endpoints include DOR sustained, disease controlled without progression of the disease (DCR), PFS, OS and safety.
+Added: DOR, PFS and OS are not yet being reported due to the data being immature as of the data cutoff date of June 20, 2024.
+Added: Follow-up evaluations with trial participants are conducted every six weeks.
+Added: The baseline characteristics of the 60 patients enrolled in the FURTHER clinical trial are
+Added: described in the following table.
+Added: As of June 20, 2024, initial interim data was available from the 45 patients who have had measurable disease at baseline by blinded independent central review committee (BICR), had received at least two tumor assessments, had progressive disease or death, or discontinued from treatment.
+Added: Of these 45 patients 23 are in the 240mg first line PACC patient group and 22 are in the 160mg first line PACC patient group.
+Added: Safety data were available for all 60 patients.
+Added: Based on these data, reduction in tumor size was observed across all cohorts.
+Added: Confirmed ORRs by BICR (defined as a reduction in tumor size of at least 30% from the baseline in a patient without evidence of progression) were 64% among the 240mg cohort and 35% among the 160 mg cohort.
+Added: Confirmed ORRs by investigator review (defined as a reduction in tumor size of at least 30% from the baseline in a patient without evidence of progression) were 68% among the 240mg cohort and 52% among the 160 mg cohort.
+Added: The disease control rate (DCR) by BICR, which includes complete responses, partial responses and stable disease, was 100% and 91% for each of these respective trial cohorts, respectively.
+Added: The extent of change in tumor size was evaluated across patients and shown in the figure below.
+Added: Median tumor size reduction of 51% was observed in the 240 mg cohort and 34% was observed in the 160 mg cohort.
+Added: Patients on average achieved greater tumor size reduction in the 240 mg dose versus the 160 mg dose.
+Added: Tumor size reduction was observed across the different PACC mutations (frequent, less frequent, single and compound mutations).
+Added: Tumor size reduction was observed in different PACC mutations with firmonertinib
+Added: Responses occurred rapidly with most patients having a partial response by the first tumor assessment at six weeks with responses ongoing in many patients as denoted in the figure below.
+Added: Confirmed CNS responses were also observed in response evaluable patients as denoted in the figure below.
+Added: Firmonertinib was observed to be generally well tolerated and demonstrated safety results similar to prior firmonertinib trials.
+Added: The table below summarizes this safety and tolerability data collected in the FURTHER trial as a whole and in Cohort 4 specifically, as of July 5, 2024:
FAVOUR — Ongoing Phase 1b Clinical Trial in NSCLC Patients with EGFR Exon 20 Insertion Mutations
−Removed: The FAVOUR clinical trial is an ongoing 90-patient, Phase 1b clinical trial being conducted by Allist in China that is intended to assess the safety and efficacy of furmonertinib in locally advanced or metastatic NSCLC patients who have EGFR exon 20 insertion mutations.
+Added: The FAVOUR clinical trial is a 90-patient, Phase 1b clinical trial being conducted by Allist in China that is intended to assess the safety and efficacy of firmonertinib in locally advanced or metastatic NSCLC patients who have EGFR exon 20 insertion mutations.
This 90-patient clinical trial consists of 3 treatment cohorts of 30 patients each.
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Patients with asymptomatic metastases involving the CNS are allowed to participate in the trial.
−Removed: First-line patients receive 240 mg furmonertinib once daily.
−Removed: Patients that have received prior treatment are randomized to receive either 160 mg or 240 mg of furmonertinib once daily.
−Removed: The primary endpoint of this trial is ORR as measured by the Response Evaluation Criteria In Solid Tumors (version 1.1) by Blinded Independent Central Review.
+Added: First-line patients receive 240 mg firmonertinib once daily.
+Added: Patients that have received prior treatment are randomized to receive either 160 mg or 240 mg of firmonertinib once daily.
+Added: The primary endpoint of this trial is ORR as measured by the RECIST version 1.1 by BICR.
Secondary endpoints include DOR sustained, disease controlled without progression of the disease (DCR), PFS, overall survival (OS) and safety.
−Removed: OS is not reported due to the data being immature as of the data cutoff date of June 15, 2023.
+Added: OS is not reported due to the
+Added: data being immature as of the data cutoff date of June 15, 2023.
Follow-up evaluations with trial participants are conducted every six weeks.
−Removed: In the treatment-naïve population, furmonertinib is being evaluated as a first-line therapy.
−Removed: The baseline characteristics of the 86
−Removed: patients enrolled in the FAVOUR clinical trial as of June 15, 2023 are described in the following table.
−Removed: Allist expects to release final results of the primary analysis from the FAVOUR study in 2024.
+Added: In the treatment-naïve population, firmonertinib is being evaluated as a first-line therapy.
+Added: The baseline characteristics of the 86 patients enrolled in the FAVOUR clinical trial as of June 15, 2023 are described in the following table.
Eastern Cooperative Oncology Group performance status scale
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Tumor size reduction was observed across the different locations of the exon 20 insertion (near loop, far loop and helical mutations).
−Removed: Tumor size reduction was observed in all EGFR exon 20 insertion mutation subtypes with furmonertinib
+Added: Tumor size reduction was observed in all EGFR exon 20 insertion mutation subtypes with firmonertinib
Responses occurred rapidly with most patients having a partial response by the first tumor assessment at six weeks with responses ongoing in many patients as denoted in the figure below.
−Removed: Furmonertinib was observed to be generally well tolerated and demonstrated safety results similar to prior furmonertinib trials.
+Added: Firmonertinib was observed to be generally well tolerated and demonstrated safety results similar to prior firmonertinib trials.
As of June 15, 2023, the following six (n=86) TRSAEs were observed:
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SHP2 is a protein tyrosine phosphatase that has an important role in the signaling pathway downstream of EGFR.
−Removed: Activating SHP2 mutations have been observed in breast, lung and colorectal cancers, among others, which underscores the central role of SHP2 in tumor cells in transmitting growth signals to rat sarcoma RAS (see figure below).
+Added: Activating SHP2 mutations have been observed in breast, lung and colorectal cancers, among others, which underscores the central role of SHP2 in tumor cells in transmitting growth signals to rat sarcoma RAS.
Besides transmitting growth signals from EGFR, SHP2 also participates in signal transduction processes of other receptor tyrosine kinase that can confer resistance to EGFR TKI such as MET.
In preclinical EGFRm NSCLC tumor xenograft models small molecular inhibitors of SHP2 can further potentiate the activity of EGFR TKI and overcome resistance conferred by activated MET signaling.
−Removed: We therefore believe that the combination of furmonertinib with a potent and specific SHP2 inhibitor may further potentiate furmonertinib activity and prevent the outgrowth of resistant tumor cells.
−Removed: We have therefore initiated a Phase 1b clinical trial combining furmonertinib with a SHP2 inhibitor ICP-189 being developed by InnoCare.
−Removed: Preclinical studies with osimertinib demonstrated the encouraging activity of this combination
−Removed: in preventing resistance from developing and we believe similar results will be obtained in preclinical studies with furmonertinib based on a common mechanism of action.
−Removed: The Phase 1b trial is designed to evaluate the safety, pharmacokinetics and preliminary efficacy of the furmonertinib-ICP-189 combination in EGFRm NSCLC involving classical mutations and we dosed the first patient in March 2024.
−Removed: An expansion cohort in patients previously treated with a third-generation EGFR TKI is planned once a dose and schedule for drug administration has been determined, with potential proof of concept in second-line classical EGFRm NSCLC in 2026, and 2027 in a planned EGFR-TKI naïve first-line therapy cohort.
+Added: We therefore believe that the combination of firmonertinib with a potent and specific SHP2 inhibitor may further potentiate firmonertinib activity and prevent the outgrowth of resistant tumor cells.
+Added: We have therefore initiated a Phase 1b clinical trial combining firmonertinib with a SHP2 inhibitor ICP-189 being developed by InnoCare.
+Added: Preclinical studies with osimertinib demonstrated the encouraging activity of this combination in preventing resistance from
+Added: developing and we believe similar results will be obtained in preclinical studies with firmonertinib based on a common mechanism of action.
+Added: The Phase 1b trial is designed to evaluate the safety, pharmacokinetics and preliminary efficacy of the firmonertinib-ICP-189 combination in EGFRm NSCLC involving classical mutations and we dosed the first patient in March 2024.
+Added: An expansion cohort in patients previously treated with a third-generation EGFR TKI is initiated with potential proof of concept in second-line classical EGFRm NSCLC expected to become available in 2026 .
Planned Adjuvant Study in NSCLC Patients with Uncommon EGFRm, including Exon 20 Insertion and PACC Mutations
−Removed: We intend to initiate a single multicenter, randomized, global pivotal Phase 3 clinical trial to investigate the potential benefit of furmonertinib when administered to adult patients with Stage Ib to IIIa EGFRm NSCLC, after surgical resection.
−Removed: We intend to restrict eligibility in this clinical trial to patients with uncommon EGFR mutations including PACC, exon 20 insertion and other uncommon EGFRm.
−Removed: Participants are to be randomized on a 1:1 basis to receive either furmonertinib or placebo for three years and stratified based on stage of disease, mutation type and geographic origin.
−Removed: Participants are to receive furmonertinib daily over a three-year period with the primary endpoint to be disease free survival with secondary endpoints being OS and safety.
−Removed: We are targeting enrollment into this clinical trial to commence in 2026.
+Added: We intend to participate in a single multicenter, randomized, global pivotal Phase 3 clinical trial initiated in China to investigate the potential benefit of firmonertinib when administered to adult patients with Stage Ib to IIIb EGFRm NSCLC, after surgical resection.
+Added: Eligibility in this clinical trial is restricted to patients with uncommon EGFR mutations including PACC, exon 20 insertion and other uncommon EGFRm.
+Added: Participants are to be randomized on a 1:1 basis to receive either firmonertinib or placebo for three years and stratified based on stage of disease, mutation type and geographic origin.
+Added: Participants are to receive firmonertinib daily over a three-year period with the primary endpoint to be disease free survival with secondary endpoints being OS and safety.
+Added: We intend to participate in this clinical trial in 2026.
FURLONG — Completed Phase 3 Clinical Trial in Classical EGFRm First-Line NSCLC Patients
−Removed: FURLONG was a 358-patient randomized, double-blinded, multi-center clinical trial with an active control arm, conducted in China by Allist, designed to compare the safety and efficacy of once daily dosing of 80 mg furmonertinib to 250 mg of gefitinib as first-line therapy in patients with locally advanced or metastatic NSCLC with classical EGFRm.
−Removed: Data from this trial supported the 2022 approval of furmonertinib in China for this patient population.
−Removed: The 358 patients enrolled in this Phase 3 trial were randomized on a 1:1 basis to receive either 80 mg of furmonertinib or 250 mg gefitinib orally as monotherapy in three-week cycles.
+Added: FURLONG was a 358-patient randomized, double-blinded, multi-center clinical trial with an active control arm, conducted in China by Allist, designed to compare the safety and efficacy of once daily dosing of 80 mg firmonertinib to 250 mg of gefitinib as first-line therapy in patients with locally advanced or metastatic NSCLC with classical EGFRm.
+Added: Data from this trial supported the 2022 approval of firmonertinib in China for this patient population.
+Added: The 358 patients enrolled in this Phase 3 trial were randomized on a 1:1 basis to receive either 80 mg of firmonertinib or 250 mg gefitinib orally as monotherapy in three-week cycles.
All patients in the FURLONG clinical trial had either advanced Stage 3 or Stage 4 disease.
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Eastern Cooperative Oncology Group performance status scale
−Removed: Furmonertinib demonstrated improved efficacy results as compared to gefitinib in the FURLONG clinical trial
−Removed: Furmonertinib demonstrated clinically meaningful and statistically significant therapeutic benefit as compared to gefitinib in the FURLONG clinical trial.
−Removed: In this clinical trial, we saw patients with furmonertinib lived longer without progression of disease.
−Removed: Median PFS in the patient cohort that was treated with furmonertinib was 20.8 months as compared to 11.1 months for the cohort that received gefitinib, representing a hazard ratio of 0.443 with p value <0.0001.
−Removed: The ORR in the furmonertinib cohort, which included clinical trial participants exhibiting either a complete
+Added: Firmonertinib demonstrated improved efficacy results as compared to gefitinib in the FURLONG clinical trial
+Added: Firmonertinib demonstrated clinically meaningful and statistically significant therapeutic benefit as compared to gefitinib in the FURLONG clinical trial.
+Added: In this clinical trial, we saw patients with firmonertinib lived longer without progression of disease.
+Added: Median PFS in the patient cohort that was treated with firmonertinib was 20.8 months as compared to 11.1 months for the cohort that received gefitinib, representing a hazard ratio of 0.443 with p value <0.0001.
+Added: The ORR in the firmonertinib cohort, which included clinical trial participants exhibiting either a complete
response or a partial response to therapy, was 89% as compared to 84% in the gefitinib arm of the trial.
The Kaplan-Meier curve of progression free survival in both cohorts is illustrated in the chart presented below.
−Removed: Furmonertinib demonstrated improved safety results as compared to gefitinib in the FURLONG clinical trial
−Removed: Furmonertinib also demonstrated favorable safety results as compared to gefitinib in the FURLONG clinical trial.
−Removed: Despite an extended median duration of exposure to furmonertinib of 18.3 months as compared to 11.2 months among patients in the gefitinib cohort, furmonertinib administration resulted in fewer Grade 3 TRAEs as compared to gefitinib, 11.2% versus 17.9%, and fewer treatment-related serious adverse events, 5.6% versus 6.1%.
+Added: Firmonertinib demonstrated improved safety results as compared to gefitinib in the FURLONG clinical trial
+Added: Firmonertinib also demonstrated favorable safety results as compared to gefitinib in the FURLONG clinical trial.
+Added: Despite an extended median duration of exposure to firmonertinib of 18.3 months as compared to 11.2 months among patients in the gefitinib cohort, firmonertinib administration resulted in fewer Grade 3 TRAEs as compared to gefitinib, 11.2% versus 17.9%, and fewer treatment-related serious adverse events, 5.6% versus 6.1%.
The following TRSAEs were observed in ten patients (n=178) in the FURLONG study:
3 unchanged sentences
The rate of trial discontinuation related to TRAEs was 3.4%, with six trial patients ending trial participation because of AEs, one as a result of each of interstitial lung disease, hyperbilirubinemia, visual impairment, ECG QT prolongation, ALT/AST elevation and decreased platelet count.
−Removed: Furmonertinib exhibited superior efficacy results in the treatment of CNS metastases in the FURLONG clinical trial
+Added: Firmonertinib exhibited superior efficacy results in the treatment of CNS metastases in the FURLONG clinical trial
Of the 358 patients enrolled in FURLONG, 60 had measurable CNS lesions that could be evaluated.
−Removed: Among trial participants with measurable CNS metastases, furmonertinib produced a confirmed CNS metastases specific ORR of 91% vs.
+Added: Among trial participants with measurable CNS metastases, firmonertinib produced a confirmed CNS metastases specific ORR of 91% vs.
65% for gefitinib.
−Removed: In the full analysis set of 133 patients who had measurable or non-measurable CNS metastases the median CNS metastases specific progression free survival was 20.8 months for furmonertinib versus 9.8 months for the cohort that received gefitinib.
−Removed: Additionally, in a post-hoc analysis of patients that did not present with CNS lesions at enrollment, none of the patients who were treated with furmonertinib developed new lesions related to CNS metastases during the trial period.
+Added: In the full analysis set of 133 patients who had measurable or non-measurable CNS metastases the median CNS metastases specific progression free survival was 20.8 months for firmonertinib versus 9.8 months for the cohort that received gefitinib.
+Added: Additionally, in a post-hoc analysis of patients that did not present with CNS lesions at enrollment, none of the patients who were treated with firmonertinib developed new lesions related to CNS metastases during the trial period.
Among gefitinib patients, 8 trial participants developed such lesions.
−Removed: We believe this difference reflects furmonertinib’s enhanced potential to cross the blood-brain barrier which we believe may enable the prevention of CNS metastases.
−Removed: Molecular Structure of Furmonertinib
−Removed: The molecular structure of furmonertinib is shown below.
−Removed: Furmonertinib contains an acrylamide side chain to confer irreversible binding to the EGFR kinase domain that may result in prolonged target inhibition and a flexible trifluoroethoxy side chain linked to a pyridine to provide additional contact points in the drug binding pocket, which we believe may enable improved binding across EGFR mutants as modeled below.
−Removed: It is believed that these two features of furmonertinib work together to enable broad inhibition of both classical and uncommon EGFR mutations such as exon 20 insertions and PACC mutations.
−Removed: In addition, the active metabolite of furmonertinib, AST5902 retained mutation specificity in vitro , which we believe may minimize toxicity due to EGFR inhibition in non-cancer cells.
−Removed: The molecular structure of furmonertinib contains numerous advantageous features
−Removed: The chemical structure of Furmonertinib
+Added: We believe this difference reflects firmonertinib’s enhanced potential to cross the blood-brain barrier which we believe may enable the prevention of CNS metastases.
+Added: Molecular Structure of Firmonertinib
+Added: The molecular structure of firmonertinib is shown below.
+Added: Firmonertinib contains an acrylamide side chain to confer irreversible binding to the EGFR kinase domain that may result in prolonged target inhibition and a flexible trifluoroethoxy side chain linked to a pyridine to provide additional contact points in the drug binding pocket, which we believe may enable improved binding across EGFR mutants as modeled below.
+Added: It is believed that these two features of firmonertinib work together to enable broad inhibition of both classical and uncommon EGFR mutations such as exon 20 insertions and PACC mutations.
+Added: In addition, the active metabolite of firmonertinib, AST5902 retained mutation specificity in vitro , which we believe may minimize toxicity due to EGFR inhibition in non-cancer cells.
+Added: The molecular structure of firmonertinib contains numerous advantageous features
+Added: The chemical structure of Firmonertinib
A trifluoroethoxy side chain was included to provide additional contact points across different EGFR mutant subtypes
−Removed: Our Aarvik Antibody Drug Conjugate Collaboration
+Added: Our Antibody Drug Conjugate Collaborations
ADCs have emerged as an important therapeutic approach to delivering potent chemotherapy more directly to tumor cells which express a target on its cell surface while avoiding toxicity to normal cells which express the target at lower levels.
−Removed: However, currently available ADCs that utilize conventional antibodies that bind a single target as the drug delivery vehicle are still plaqued by dose limiting and chronic toxicities.
+Added: However, currently available ADCs that utilize conventional antibodies that bind a single target as the drug delivery vehicle are still plagued by dose limiting and chronic toxicities.
In addition target expression tends to be heterogeneous within a tumor which can limit efficacy and/or restrict ADC use to only tumors that have high and mostly homogenous target expression.
+Added: Our Aarvik Antibody Drug Conjugate Collaboration
To overcome the limitations of conventional ADCs we are advancing the development of next-generation ADCs through a research collaboration with Aarvik.
Leveraging Aarvik’s proprietary multi-target, multivalent antibody and site-specific conjugation platform, we have an ongoing research collaboration in an effort to develop an ADC that is potentially both safer and more effective than a conventional single target bivalent ADC.
−Removed: We anticipate identification of a lead candidate for IND-enabling studies in late 2024 or early 2025.
+Added: We identified a lead candidate (ARR-002) and initiated IND-enabling activities.
+Added: Our Alphamab Antibody Drug Conjugate Collaboration
+Added: In addition to our Aarvik ADC Collaboration, we established an ADC collaboration with Alphamab in June 2024.
+Added: We are working with Alphamab to leverage their proprietary linker-payload platform and glycan-conjugation technology to identify novel ADCs for oncology indications globally, except greater China, which includes mainland China, Hong Kong, Macau and Taiwan where Alphamab retains the right to develop and commercialize ADCs.
+Added: Our Lepu Biopharma Antibody Drug Conjugate Collaboration
+Added: We also established an ADC collaboration with Lepu Biopharma in January 2025, to gain ex-Greater China, which includes mainland China, Hong Kong, Macau and Taiwan, rights to ARR-217.
Licenses, Partnerships and Collaborations
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Global Technology Transfer and License Agreement
−Removed: On June 30, 2021 (the Effective Date), we entered into a Global Technology Transfer and License Agreement with Allist, as amended on November 6, 2023 (the Allist License Agreement), pursuant to which (i) Allist granted to us an exclusive (even as to Allist and its affiliates), royalty-bearing, sublicensable license under certain intellectual property (including patents and know-how) owned or controlled by Allist to develop, manufacture and commercialize any product (the Licensed Product) containing furmonertinib or any of its salts or derivatives as an active ingredient (the Licensed Compound), for all uses (the Field), in all countries and territories (the Licensed Territory) other than greater China, which includes mainland China, Hong Kong, Macau and Taiwan (the Retained Territory);
+Added: On June 30, 2021 (the Effective Date), we entered into a Global Technology Transfer and License Agreement with Allist, as amended on November 6, 2023 (the Allist License Agreement), pursuant to which (i) Allist granted to us an exclusive (even as to Allist and its affiliates), royalty-bearing, sublicensable license under certain intellectual property (including patents and know-how) owned or controlled by Allist to develop, manufacture and commercialize any product (the Licensed Product) containing firmonertinib or any of its salts or derivatives as an active ingredient (the Licensed Compound), for all uses (the Field), in all countries and territories (the Licensed Territory) other than greater China, which includes mainland China, Hong Kong, Macau and Taiwan (the Retained Territory);
and (ii) we granted Allist a non-exclusive sublicensable license to use (1) any information, data and results that relate solely and exclusively to the Licensed Product and which we generate or collect in the conduct of clinical trials or preclinical activities in the Licensed Territory and (2) any improvements or enhancements that we make or discover under the License Agreement to the know-how licensed to us and is owned or controlled by us, to develop, manufacture, and commercialize the Licensed Compound and the Licensed Product for all uses in the Retained Territory.
The parties have appointed a joint collaboration committee, comprised of representatives from both us and Allist (the Collaboration Committee), to oversee the parties’ development activities related to the Licensed Compound under the Allist License Agreement.
−Removed: Under the terms of the Allist License Agreement, we are required to use commercially reasonable efforts to (i) develop the Licensed Product in the Licensed Territory, (ii) prepare and submit regulatory filings and seek regulatory approvals in all major market countries in the Licensed Territory and (iii) perform all commercialization activities for the Licensed Product in each country in the Licensed Territory in which the Licensed Product has received regulatory approval, and we are solely responsible for all the expenses associated with the foregoing (i)-(iii).
+Added: Under the terms of the Allist License Agreement, we are required to use commercially reasonable efforts to (i) develop the Licensed Product in the Licensed Territory, (ii) prepare and submit regulatory filings and seek regulatory
+Added: approvals in all major market countries in the Licensed Territory and (iii) perform all commercialization activities for the Licensed Product in each country in the Licensed Territory in which the Licensed Product has received regulatory approval, and we are solely responsible for all the expenses associated with the foregoing (i)-(iii).
We are also responsible for the manufacture and supply of the Licensed Product in the Licensed Territory, by ourselves or through a third-party manufacturer, for the purpose of conducting clinical trials, obtaining regulatory approval and commercializing the Licensed Product in the Licensed Territory.
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As additional consideration for the licenses and rights granted to us under the Allist License Agreement, we made an upfront, non-creditable and non-refundable cash payment of $40.0 million to Allist on the Effective Date (the Initial Payment).
−Removed: We are obligated to make development and regulatory approval milestone payments to Allist upon the
−Removed: achievement of specific milestone events related to the Licensed Product in an aggregate amount up to $110.0 million, and commercial milestone payments to Allist upon the achievement of specified net sales thresholds of the Licensed Product in an aggregate amount up to $655.0 million.
+Added: We are obligated to make development and regulatory approval milestone payments to Allist upon the achievement of specific milestone events related to the Licensed Product in an aggregate amount up to $110.0 million, and commercial milestone payments to Allist upon the achievement of specified net sales thresholds of the Licensed Product in an aggregate amount up to $655.0 million.
In 2023, we made a $5.0 million payment to Allist after we met a clinical milestone under the Allist License Agreement.
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Pursuant to the Allist Collaboration Agreement, if either party or both parties wish to jointly conduct a Global Study, one or both parties (as the case may be) shall prepare and submit the proposed strategy, protocol design, budget, proposal for budget sharing and internal process timeline for such proposed Global Study to the Collaboration Committee that was appointed pursuant to the Allist License Agreement for its review at least 90 days in advance of the applicable protocol filing with the relevant regulatory authorities.
−Removed: Upon the approval by the collaboration committee of a development plan for the proposed Global Study that includes the allocation of the sponsorship for the conduct of the proposed Global Study and other details for conducting the proposed Global Study as specified in the Allist Collaboration Agreement, the proposed Global Study shall be deemed to be a “Joint Global Study” and such development plan a “Joint Global Development Plan.” The parties have agreed in the Allist Collaboration Agreement that (i) we will be the sponsor of any Joint Global Study in the Licensed Territory (as defined in the Allist License Agreement), (ii) Allist will be the sponsor of any Joint Global Study in the PRC (as defined in the Allist License Agreement) and (iii) the Collaboration Committee shall designate the party that will be the sponsor of any Joint Global Study in certain territories (Joint Territories).
+Added: Upon the approval by the collaboration committee of a development plan for the proposed Global Study that includes the allocation of the sponsorship for the conduct of the proposed Global Study and other details for conducting the proposed Global Study as specified in the Allist Collaboration Agreement, the proposed Global Study shall be deemed to be a “Joint Global Study” and such development plan a “Joint Global Development Plan.” The parties have agreed in the Allist Collaboration Agreement that (i) we will be the sponsor of any Joint Global Study in the Licensed Territory (as defined in the Allist License Agreement), (ii) Allist will be the sponsor of any Joint Global Study in the PRC (as defined in the Allist License Agreement) and (iii) the Collaboration Committee shall designate the party that
+Added: will be the sponsor of any Joint Global Study in certain territories (Joint Territories).
The parties will mutually agree on the global regulatory strategy for each Joint Global Study.
4 unchanged sentences
On December 21, 2021, we entered into a Research Collaboration Agreement, as amended effective June 30, 2023 (the Aarvik Collaboration Agreement), with Aarvik, pursuant to which we and Aarvik agreed to collaborate on the discovery and characterization of novel ADCs with a goal to identify ADCs that may be suitable for further development by us in accordance with the applicable statements of work (each a SOW, collectively, the SOWs) until the completion of all activities in accordance with the applicable SOWs (collectively, the Aarvik Collaboration).
−Removed: The parties have appointed a joint research committee, comprised of our representatives and representatives from Aarvik, to oversee the parties’ research collaboration activities under the Aarvik Collaboration Agreement.
−Removed: Aarvik has agreed, during the term of the Aarvik Collaboration and following our exercise of the Option (as defined herein), to certain exclusivity and ownership provisions with respect to ADCs.
−Removed: Under the Aarvik Collaboration Agreement, Aarvik has granted us an exclusive option (the Option) to obtain the exclusive rights to certain of Aarvik’s intellectual property and the option to acquire certain of Aarvik’s intellectual property for the research, development, manufacture, use, commercialization, or other exploitation of the ADCs related to (i) the two agreed targets to which the compounds being developed under the Aarvik Collaboration bind, which we refer to as the Target Pair and (ii) one of the targets in the Target Pair in certain indications, and to acquire certain intellectual property generated during the Aarvik Collaboration (Collaboration IP).
−Removed: We have not yet selected the indication or indications that we would pursue in the collaboration and anticipate doing so in connection with the identification of a lead candidate for IND-enabling studies.
−Removed: Upon our exercise of the Option, if made, we will have the exclusive and worldwide right to develop, manufacture and commercialize any product containing an ADC generated within the Aarvik Collaboration, as well as antibodies incorporated into such ADC.
−Removed: Under the Aarvik Collaboration Agreement, we are required to pay Aarvik a collaboration execution fee and research fees as provided in the SOWs in an aggregate of up to $3.4 million (based on estimated research fees), of which we have incurred $1.7 million through December 31, 2023.
+Added: On August 9, 2024, we entered into an amendment and restatement of the Aarvik Collaboration Agreement (the Amended and Restated Aarvik Collaboration Agreement).
+Added: Under the Amended and Restated Aarvik Collaboration Agreement, Aarvik granted us an exclusive option (the Option) to obtain exclusive rights to certain of Aarvik’s intellectual property for the research, development, manufacture, use, commercialization, or other exploitation of the novel ADCs.
+Added: Under the Amended and Restated Aarvik Collaboration Agreement, we are required to pay Aarvik a collaboration initiation fee and research fees as provided in the SOWs.
+Added: We exercised the exclusive option simultaneously with entry into the Amended and Restated Aarvik Collaboration Agreement.
+Added: The parties have appointed a joint research committee, comprised of our representatives and representatives from Aarvik, to oversee the parties’ research collaboration activities under the Amended and Restated Aarvik Collaboration Agreement.
+Added: Aarvik has agreed, during the term of the Aarvik Collaboration and following our exercise of the Option, to certain exclusivity and ownership provisions with respect to ADCs.
+Added: Under the Amended and Restated Aarvik Collaboration Agreement, we are required to pay Aarvik a collaboration execution fee and research fees as provided in the SOWs.
+Added: We have incurred $4.9 million of fees through December 31, 2024.
We further agreed to reimburse Aarvik for actual costs incurred in procuring other materials Aarvik will actually use in performing activities under the applicable SOWs.
−Removed: If we exercise the Option, we are required to make a one-time non-refundable option exercise payment of low single-digit millions and we will be obligated to make milestone payments to Aarvik upon the achievement of specific regulatory and sales milestone events related to the Aarvik Collaboration as specified and determined in the Aarvik Collaboration Agreement.
+Added: Because we have exercised the Option, we were required to make a one-time non-refundable option exercise payment of low single-digit millions and we will be obligated to make milestone payments to Aarvik upon the achievement of specific regulatory and sales milestone events related to the Aarvik Collaboration as specified and determined in the Amended and Restated Aarvik Collaboration Agreement.
Combined regulatory milestone payments and sales milestone payments will not exceed $98.0 million per product.
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Our obligation to pay royalties for each product, calculated on a product-by-product and jurisdiction-by-jurisdiction basis, begins from the date of the first commercial sale of each product within a given jurisdiction and extends until the earliest of (a) the first approval of a biosimilar product related to such product in such jurisdiction, which is made and sold by a different company, meeting specific government regulatory standards, (b) an anniversary of the date of the first commercial sale of such product in such jurisdiction, or (c) the expiration of the last valid claim of a patent included in the Collaboration IP that pertains to the any ADC generated within Aarvik Collaboration or any derivative thereof featured in such product within such jurisdiction (the Aarvik Collaboration Royalty Term).
−Removed: If we exercise the Option, we must use commercially reasonable efforts to (a) file an IND within 24 months of completion of Aarvik’s transfer of certain documentation relating to Aarvik’s intellectual property;
−Removed: and (b) initiate a Phase 2 clinical trial within 24 months after completion of a Phase 1 Clinical Trial, or initiate a Phase 2b Clinical Trial within 24 months after completion of a combined Phase 1/2 a Clinical Trial;
−Removed: in each case subject to certain exceptions.
−Removed: If we fail to use commercially reasonable efforts to meet these key milestones with respect to an agreed Target Pair, then Aarvik’s sole remedy is for us to assign back to Aarvik the Collaboration IP as it relates to the Target Pair.
−Removed: The Aarvik Collaboration Agreement will remain in full force and effect until the expiration of all Aarvik Collaboration Royalty Terms for all products under the Aarvik Collaboration Agreement, unless terminated earlier.
−Removed: On a jurisdiction-by-jurisdiction and product-by-product basis, following the expiration of the Aarvik Collaboration Royalty
−Removed: Term, the license granted to us hereunder will become nonexclusive, perpetual, irrevocable, fully-paid and royalty-free.
−Removed: The Aarvik Collaboration Agreement will terminate if we do not exercise the Option during the option period.
−Removed: We can terminate the Aarvik Collaboration Agreement for convenience after we exercise the Option.
−Removed: Either party can terminate the Aarvik Collaboration Agreement for material breach that is not cured within a specified period, or for the other party’s insolvency or certain bankruptcy events.
−Removed: Upon termination of the Aarvik Collaboration Agreement with respect to the Target Pair or any given product, the licenses granted by Aarvik will terminate with respect to the applicable terminated Target Pair or product, and unless the Aarvik Collaboration Agreement is terminated by us for Aarvik’s uncured breach or insolvency, then the Collaboration IP will be assigned back to Aarvik.
−Removed: If the Aarvik Collaboration Agreement is terminated only with respect to a particular jurisdiction (but not all jurisdictions) and a specific Target Pair or product, then we will grant to Aarvik an exclusive and fully paid-up right and license to use the Collaboration IP with respect to the terminated Target Pair or product in such jurisdiction.
+Added: The Amended and Restated Aarvik Collaboration Agreement will remain in full force and effect until the expiration of all Aarvik Collaboration Royalty Terms for all products under the Amended and Restated Aarvik Collaboration Agreement, unless terminated earlier.
+Added: On a jurisdiction-by-jurisdiction and product-by-product basis, following the expiration of the Aarvik Collaboration Royalty Term, the license granted to us hereunder will become nonexclusive, perpetual, irrevocable, fully-paid and royalty-free.
+Added: We can terminate the Amended and Restated Aarvik Collaboration Agreement for convenience.
+Added: Either party can terminate the Amended and Restated Aarvik Collaboration Agreement for material breach that is not cured within a specified period, or for the other party’s insolvency or certain bankruptcy events.
+Added: Upon termination of the Amended and Restated Aarvik Collaboration Agreement with respect to the Target Pair or any given product, the licenses granted by Aarvik will terminate with respect to the applicable terminated Target Pair or product, and unless the Amended and Restated Aarvik Collaboration Agreement is terminated by us for Aarvik’s uncured breach or insolvency, then the Collaboration IP will be assigned back to Aarvik.
+Added: If the Amended and Restated Aarvik Collaboration Agreement is terminated only with respect to a particular jurisdiction (but not all jurisdictions) and a specific Target Pair or product, then we will grant to Aarvik an exclusive and fully paid-up right and license to use the licensed IP with respect to the terminated Target Pair or product in such jurisdiction.
InnoCare Clinical Collaboration Agreement
−Removed: On June 23, 2023, we entered into a Clinical Collaboration Agreement (the InnoCare Collaboration Agreement) with InnoCare, pursuant to which we and InnoCare agreed to contribute resources to a clinical trial evaluating the use of furmonertinib in combination with InnoCare’s ICP-189, a SHP2i (the InnoCare Collaboration Clinical Trial).
+Added: On June 23, 2023, we entered into a Clinical Collaboration Agreement (the InnoCare Collaboration Agreement) with InnoCare, pursuant to which we and InnoCare agreed to contribute resources to a clinical trial evaluating the use of firmonertinib in combination with InnoCare’s ICP-189, a SHP2i (the InnoCare Collaboration Clinical Trial).
Pursuant to the InnoCare Collaboration Agreement, we and InnoCare have mutually granted to each other a non-exclusive license to certain of the granting party’s intellectual property solely for the purpose of conducting the InnoCare Collaboration Clinical Trial.
−Removed: Under the InnoCare Collaboration Agreement, InnoCare has the right to use furmonertinib solely for the InnoCare Collaboration Clinical Trial.
+Added: Under the InnoCare Collaboration Agreement, InnoCare has the right to use firmonertinib solely for the InnoCare Collaboration Clinical Trial.
We and InnoCare have agreed that InnoCare is the regulatory sponsor for the InnoCare Collaboration Clinical Trial and has the sole right and responsibility to prepare all regulatory filings related to the InnoCare Collaboration Clinical Trial, including the protocol and IND filings, conduct the InnoCare Collaboration Clinical Trial, and communicate with regulatory authorities with respect to the InnoCare Collaboration Clinical Trial.
4 unchanged sentences
The final report and any raw data (collectively, the InnoCare Collaboration Report) from the InnoCare Collaboration Clinical Trial are jointly owned by us and InnoCare.
−Removed: We may not, without InnoCare’s prior consent, use the InnoCare Collaboration Report for purposes of developing or commercializing ICP- 189 alone or in combination with furmonertinib.
−Removed: InnoCare may not, without our prior consent, use the InnoCare Collaboration Report for purposes of developing or commercializing furmonertinib alone or in combination with ICP-189.
+Added: We may not, without InnoCare’s prior consent, use the InnoCare Collaboration Report for purposes of developing or commercializing ICP- 189 alone or in combination with firmonertinib.
+Added: InnoCare may not, without our prior consent, use the InnoCare Collaboration Report for purposes of developing or commercializing firmonertinib alone or in combination with ICP-189.
Under the InnoCare Collaboration Agreement, we and InnoCare have agreed to equally share all incurred costs associated with the InnoCare Collaboration Clinical Trial in accordance with a mutually agreed upon budget and have agreed to provide each other with periodic expense reports detailing costs related to the InnoCare Collaboration Clinical Trial.
1 unchanged sentence
We and InnoCare have agreed to discuss such expense reports and determine the calculation of net amounts owed by one party to the other to ensure the appropriate equal sharing of costs associated with the InnoCare Collaboration Clinical Trial.
−Removed: If we or InnoCare become aware of any costs that may be in excess of the costs set out in the budget for the InnoCare Collaboration Clinical Trial, then the respective party shall notify the other party and we and InnoCare shall discuss such costs in order to determine if such costs are permissible.
+Added: If we or InnoCare become aware of any costs that may be in excess of the costs set out in the budget for the InnoCare Collaboration Clinical Trial, then the respective party shall notify the other party and we and InnoCare shall discuss such costs in order to determine
+Added: if such costs are permissible.
InnoCare shall have the sole right to make the final decision on matters relating to the excess costs related to the InnoCare Collaboration Clinical Trial;
−Removed: however, we maintain the right to opt out of
−Removed: participating in the InnoCare Collaboration Clinical Trial if the costs surpass a certain threshold above the budget, provided that we will not have rights to the InnoCare Collaboration Report.
+Added: however, we maintain the right to opt out of participating in the InnoCare Collaboration Clinical Trial if the costs surpass a certain threshold above the budget, provided that we will not have rights to the InnoCare Collaboration Report.
The InnoCare Collaboration Agreement will remain in full force and effect until the delivery of the InnoCare Collaboration Report, unless terminated earlier.
1 unchanged sentence
The InnoCare Collaboration Agreement may also be terminated immediately by either party if either one believes that there is a material safety issue in the conduct of the InnoCare Collaboration Clinical Trial that cannot be resolved by a protocol amendment satisfactory to both parties after discussion thereof.
+Added: Alphamab Collaboration
+Added: On June 4, 2024, we entered into a Research and Collaboration Agreement with Alphamab, a wholly owned subsidiary of Alphamab Oncology, pursuant to which the Company and Alphamab will discover, develop and commercialize novel antibody drug conjugates for the treatment of cancers (the Alphamab Agreement).
+Added: Under the Alphamab Agreement, and subject to our payment to Alphamab of the applicable research costs, Alphamab will grant us an exclusive, royalty-bearing, sublicensable license under certain Alphamab intellectual property and joint intellectual property to develop and commercialize such products in all fields of use worldwide, except greater China, which includes mainland China, Hong Kong, Macau and Taiwan (the “Retained Territory”).
+Added: Alphamab retains the right to develop and commercialize such products in the Retained Territory.
+Added: Under the Alphamab Agreement, we granted to Alphamab a royalty-free, perpetual license, which is exclusive during the term of the Alphamab Agreement and non-exclusive thereafter, under all intellectual property rights conceived, discovered, developed or otherwise made solely by us or jointly with Alphamab pursuant to the activities under the Alphamab Agreement for any and all purposes within the Retained Territory.
+Added: Upon commencement of activities to manufacture the products for use in certain clinical trials, Alphamab will grant us a royalty-bearing license under certain Alphamab intellectual property to manufacture the applicable products.
+Added: Under the Alphamab Agreement, Alphamab is entitled to an upfront payment and potential development and sales milestone payments of up to an aggregate of $615.5 million from us.
+Added: Additionally, Alphamab is entitled to receive royalties in the low- to mid- single digit percent range on net sales of products outside greater China that may arise from the Alphamab Agreement.
+Added: The Alphamab Agreement is subject to termination (i) by either party for customary purposes, including the material breach by or bankruptcy of the other party, (ii) by us for convenience, (iii) by Alphamab due to our challenge of certain patents held by Alphamab, or (iv) by Alphamab on a product-by-product basis due to our failure to carry out certain diligence obligations or in certain instances if there is a change of control of the Company.
+Added: Lepu Agreement
+Added: On January 21, 2025, ArriVent entered into an Exclusive License Agreement (the “Lepu Biopharma Agreement”) with Lepu Biopharma, pursuant to which Lepu Biopharma granted us a right to develop and commercialize ARR-217 (MRG007), an antibody drug conjugate for gastrointestinal cancers outside greater China, which is mainland China, Hong Kong, Macau and Taiwan.
+Added: Under the Lepu Biopharma Agreement, Lepu Biopharma granted to us:
+Added: (i) an exclusive, royalty-bearing, sublicensable license under certain intellectual property owned or controlled by Lepu Biopharma, to develop, manufacture and commercialize any product containing ARR-217 for all uses in all countries and territories other than Greater China, which is mainland China, Hong Kong, Macau and Taiwan (the “ArriVent Territory”);
+Added: and (ii) a non-exclusive license under certain intellectual property controlled by Lepu Biopharma to develop, manufacture and commercialize any product containing ARR-217 for use in oncology in the ArriVent Territory.
+Added: Under the Lepu Biopharma Agreement, Lepu Biopharma is entitled to receive a one-time upfront payment and near-term milestone payments totaling $47.0 million in cash and is eligible to receive up to $1.16 billion in development, regulatory and sales milestones and tiered royalties in high single-digit to low-teen percentages on net sales in the ArriVent Territory.
+Added: The Lepu Biopharma Agreement is subject to termination:
+Added: (i) by either party, subject to specified cure periods, for the material breach by the other party or the bankruptcy or insolvency of the other party, (ii) by us for convenience, subject to a specified notice period, (iii) by Lepu Biopharma due to our challenge of certain patents controlled by Lepu Biopharma, or (iv) by Lepu Biopharma due to our failure to carry out certain diligence obligations.
Manufacturing
3 unchanged sentences
(Raybow) and WuXi SynTheAll Pharmaceutical company, Ltd.
−Removed: (WuXi STA) to supply the drug substance for furmonertinib to be used in planned clinical trials and with WuXi STA, with whom we have executed technology transfer related to the manufacture of drug product, to manufacture the clinical trial supplies of furmonertinib drug product.
+Added: (WuXi STA) to supply the drug substance for firmonertinib to be used in on-going and planned clinical trials and with WuXi STA, with whom we have executed technology transfer related to the manufacture of drug product, to manufacture the clinical trial and initial commercial launch supplies of firmonertinib drug product.
Both of our third-party contract manufacturers are located in China, but WuXi STA has manufacturing capabilities globally, including in the United States and Europe.
−Removed: We expect to enter into commercial supply agreements with WuXi STA for both drug substance and drug product prior to any potential approval of furmonertinib.
−Removed: Furmonertinib drug product is manufactured via conventional pharmaceutical processing procedures, employing commercially available excipients and packaging materials.
+Added: We expect to enter into commercial supply agreements with WuXi STA for both drug substance and drug product prior to any potential approval of firmonertinib.
+Added: We expect to rely on manufacturers in China for ARR-217 drug substance and drug product for use in initial clinical studies and also expect to rely on WuXi XDC Cayman, Inc., (WuXi XDC) for the manufacture of ARR-002 drug product and drug substances for initial clinical studies.
+Added: Firmonertinib drug product is manufactured via conventional pharmaceutical processing procedures, employing commercially available excipients and packaging materials.
The procedure and equipment employed for manufacture and analysis are consistent with standard organic synthesis or pharmaceutical production, and are transferable to a range of manufacturing facilities, if needed.
We intend to also maintain the current drug substance manufacturer as part of our supply chain strategy.
−Removed: In light of the recently introduced BIOSECURE Act, which, if enacted, would prohibit federal agencies from entering into procurement contracts with an entity that uses biotechnology equipment or services from a biotechnology company of concern, we are taking measures to strengthen our supply chain in the event that Raybow, WuXi STA or one of our other manufacturers is impacted.
+Added: The BIOSECURE Act was introduced in 2024 but has not become law, and there remains potential for its reintroduction in the current congressional session.
+Added: If reintroduced and enacted, the legislation would prohibit federal agencies from entering into procurement contracts with an entity that uses biotechnology equipment or services from a biotechnology company of concern.
+Added: Accordingly, we are taking measures to strengthen our supply chain in the event that Raybow, WuXi STA or one of our other manufacturers is impacted.
We intend to identify alternative potential manufacturers to ensure we have a sufficient stockpile of drug substance and drug product in the United States.
We will also continue to closely monitor geopolitical risk and implement additional mitigations and supply chain redundancies, as needed.
−Removed: See the risk factor entitled “We currently rely on a Chinese third party for the manufacture of furmonertinib for clinical development and expect to continue to rely on third parties for the foreseeable future.
−Removed: This reliance on third parties increases the risk that we will not have sufficient quantities of furmonertinib or such quantities at an acceptable cost, which could delay, prevent or impair our development or potential commercialization efforts.”
+Added: See the risk factor entitled “We currently rely on a Chinese third party for the manufacture of firmonertinib and ARR-217, for clinical development, and future supply of firmonertinib, and expect to continue to rely on third parties for the foreseeable future.
+Added: This reliance on third parties increases the risk that we will not have sufficient quantities of firmonertinib or ARR-217 or such quantities at an acceptable cost, which could delay, prevent or impair our development or potential commercialization efforts.”
The biotechnology and pharmaceutical industries have made substantial investments in recent years into the rapid development of novel treatments for NSCLC.
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Our competitors compete with us on the level of the technologies employed, or on the level of development of product candidates.
−Removed: In addition, many small biotechnology companies have formed collaborations with large, established companies to (i) obtain support for their research, development and commercialization of products or
−Removed: (ii) combine several treatment approaches to develop longer lasting or more efficacious treatments that may potentially directly compete with our current or future product candidates.
+Added: In addition, many small biotechnology companies have formed collaborations with large, established companies to (i) obtain support for their research, development and commercialization of products or (ii) combine several treatment approaches to develop longer lasting or more efficacious treatments that may potentially
+Added: directly compete with our current or future product candidates.
We anticipate that we will continue to face increasing competition as new therapies and combinations thereof, technologies and data emerge within the field of oncology and, furthermore, within the treatment of NSCLC.
In addition to the current standard of care treatments for patients with NSCLC, numerous commercial and academic preclinical studies and clinical trials are being undertaken by a large number of parties to assess novel technologies and product candidates.
−Removed: Companies that compete with us directly on the level of commercialization or development of product candidates targeting EGFR mutation-positive NSCLC include, but are not limited to, AstraZeneca, Johnson & Johnson, Takeda Pharmaceutical Company Limited, Blueprint Medicines Corp, Dizal Pharmaceutical, Oric Pharmaceuticals, Black Diamond Therapeutics, Inc., Taiho Pharmaceutical Co., Ltd., Boehringer Ingelheim and Bayer AG.
−Removed: In October 2023, Johnson & Johnson presented the results of the Phase 3 PAPILLON study of chemotherapy in combination the anti-EGFR anti-MET bispecific antibody amivantamab in first-line NSCLC patents with EGFR exon 20 insertion mutations, and announced in July 2023 that the PAPILLON study met its primary endpoint.
−Removed: In October 2023, Dizal Pharmaceutical and Oric Pharmaceuticals provided updates on their oral EGFR inhibitors sunvozertinib and ORIC-114, respectively, each of which is being studied in Phase 1 trials in first-line NSCLC patients with EGFR exon 20 insertion mutations.
+Added: Companies that compete with us directly on the level of commercialization or development of product candidates targeting EGFR mutation-positive NSCLC include, but are not limited to, AstraZeneca, Johnson & Johnson, Blossom Hill Therapeutics, Dizal Pharmaceutical, Oric Pharmaceuticals, Black Diamond Therapeutics, Inc., Cullinan Therapeutics, Inc., Taiho Pharmaceutical Co., Ltd., Boehringer Ingelheim and Bayer AG.
Many of our competitors, either alone or in combination with their respective strategic partners, have significantly greater financial resources and expertise in research and development, manufacturing, the regulatory approval process and marketing than we do.
9 unchanged sentences
We will also seek to rely on regulatory protection afforded through inclusion in expedited development and review, data exclusivity, market exclusivity and patent term extensions where available.
−Removed: Through our licensor Allist, we have sought and obtained patent protection in the United States and internationally related to furmonertinib.
−Removed: For furmonertinib and our future product candidates our strategy is to pursue patent protection covering compositions of matter and methods of use.
−Removed: In addition, we seek to identify additional means of obtaining patent protection including formulation and dosing regimen-related claims, which may enhance commercial success.
+Added: Through our licensor Allist, we have sought and obtained patent protection in the United States and internationally related to firmonertinib.
+Added: For firmonertinib and our future product candidates our strategy is to pursue patent protection covering compositions of matter and methods of use.
+Added: In addition, we seek to identify additional means of obtaining patent protection including formulation and dosing regimen-related claims, as well as manufacturing-related claims, which may enhance our commercial success.
We may also rely on trade secrets that may be important to the development of our business.
Trade secrets are difficult to protect and provide us with only limited protection.
−Removed: As of December 31, 2023, our intellectual property portfolio includes three issued U.S.
−Removed: patents, twelve issued foreign patents and one pending U.S.
−Removed: patent application and six pending international patent applications related to furmonertinib compositions of the matter and methods of use.
−Removed: With regard to the furmonertinib molecule itself, we exclusively license from Allist one issued patent in each of the United States, Canada, Europe, Japan and South Korea, as well as a pending U.S.
−Removed: reissue continuation patent application.
−Removed: These patents and the pending application, if issued, are expected to expire in 2035, assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, and without taking potential patent term extensions or adjustments into account.
−Removed: patent is a reissue patent covering furmonertinib, other compounds represented by a general formula, and a pharmaceutically acceptable salts;
−Removed: it also covers related pharmaceutical compositions, methods for treating an EGFR activating or resistant mutation mediated lung cancer and methods for selectively inhibiting an EGFR activating or resistant mutation over a wild-type EGFR to a lung cancer patient.
−Removed: With regard to mesylate salts of furmonertinib, we exclusively license from Allist one issued patent in each of the United States, Canada, Europe, Japan and South Korea.
−Removed: patent covers mesylate salts of furmonertinib, as well as pharmaceutical compositions, methods for preparing such mesylate salts and methods for treating a patient suffering from cancers.
+Added: As of December 31, 2024, our intellectual property portfolio for firmonertinib includes issued patents and pending patent applications in the U.S.
+Added: and internationally.
+Added: With regard to the firmonertinib molecule itself, we exclusively license from Allist two issued patents in the US, and one issued patent in each of, Canada, Europe, Japan and South Korea.
+Added: These patents are expected to expire in 2035, assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, and without taking potential patent term extensions or adjustments into account.
+Added: patents are reissue patents covering firmonertinib, other compounds represented by a general formula, and pharmaceutically acceptable salts of such compounds;
+Added: the patents also cover related pharmaceutical compositions, methods for treating an EGFR activating or resistant mutation mediated lung cancer and methods for selectively inhibiting an EGFR activating or resistant mutation over a wild-type EGFR to a lung cancer patient.
+Added: With regard to mesylate salts of firmonertinib, we exclusively license from Allist one issued patent in each of the United States, Canada, Europe, Japan and South Korea.
+Added: patent covers mesylate salts of firmonertinib, as well as pharmaceutical compositions, methods for preparing such mesylate salts and methods for treating a patient suffering from cancers.
With regard to crystalline forms, we also exclusively license from Allist one issued patent in each of the United States, Canada, Europe, Japan and South Korea.
−Removed: patent covers two crystaline forms of mesylate salts of furmonertinib, as well as pharmaceutical compositions, methods for preparing such crystaline forms, and methods for treating a patient suffering from cancers.
+Added: patent covers two crystaline forms of mesylate salts of firmonertinib, as well as pharmaceutical compositions, methods for preparing such crystaline forms, and methods for treating a patient suffering from cancers.
Collectively, these patents are expected to expire in 2037, assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees and without taking potential patent term extensions or adjustments into account.
−Removed: With regard to methods of use for furmonertinib, we exclusively license from Allist three Patent Cooperation Treaty (PCT) patent applications.
−Removed: The first two PCT patent applications relate to use of furmonertinib to treat disease, such as NSCLC, in patients (a) having exon 20 insertion mutations or (b) having an HER2 exon 20 insertion mutation and/or EGFR rare mutation, respectively, as well as pharmaceutical compositions containing therapeutically effective amounts of furmonertinib.
−Removed: The third PCT application relates to use of furmonertinib to treat disease, such as NSCLC, in patients having EGFR PACC mutations, as well as pharmaceutical compositions containing therapeutically effective amounts of furmonertinib.
−Removed: or foreign patents issued from national stage filings of the PCT patent applications are expected to expire in 2042 (first two PCTs) or 2043 (third PCT), assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees and that national phase entries are timely made based upon the pending PCT applications and without taking potential patent term extensions or adjustments into account.
−Removed: We may file additional patent applications in support of current and new clinical candidates as well as new platform and core technologies.
+Added: With regards to methods of manufacturing firmonertinib, we exclusively license from Allist two pending patent applications in each of the United States and Europe.
+Added: These applications, if issued, would expire in 2043.
+Added: With regard to methods of use for firmonertinib, we exclusively license from Allist one Patent Cooperation Treaty (PCT) patent application and two families of national stage patent applications pending in multiple countries, including United States, Canada, Europe, Japan and South Korea.
+Added: The national stage patent application families relate to use of firmonertinib to treat disease, such as NSCLC, in patients (a) having exon 20 insertion mutations or (b) having an HER2 exon 20 insertion mutation and/or EGFR rare mutation, respectively, as well as pharmaceutical compositions containing therapeutically effective amounts of firmonertinib.
+Added: The PCT application relates to use of firmonertinib to treat disease, such as NSCLC, in patients having EGFR PACC mutations, as well as pharmaceutical compositions containing therapeutically effective amounts of firmonertinib.
+Added: or foreign patents issued from the national stage applications or the national stage filings of the PCT patent application are expected to expire in 2042 (pending national stage application) or 2043 (PCT patent application), assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees and that national phase entries are timely made based upon the pending PCT applications and without taking potential patent term extensions or adjustments into account.
+Added: Aarvik has exclusively licensed us one PCT application relating to antibody scaffolds and ADCs comprising such scaffolds and two U.S.
+Added: provisional applications relating to antibody scaffolds and ADCs comprising such scaffolds, including ARR-002.
+Added: or foreign patents issued from national stage filings of the PCT patent application, and any U.S.
+Added: or foreign patents issued from the provisional application, are expected to expire in 2044 and 2045, respectively, without taking into account any patent term adjustments or extensions.
+Added: Lepu Biopharma has exclusively licensed us two PCT applications relating to antibodies and ADCs, including ARR-217.
+Added: or foreign patents issued from such application are expected to expire in 2045, without taking into account any patent term adjustments or extensions.
+Added: We may file additional patent applications in support of current and new product candidates as well as new platform and core technologies.
Our commercial success will depend in part on obtaining and maintaining patent protection and trade secret protection of our current and future product candidates and the methods used to develop and manufacture them, as well as successfully defending any such patents against third-party challenges and operating without infringing on the proprietary rights of others.
5 unchanged sentences
In the United States, a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the U.S.
−Removed: Patent and Trademark Office (USPTO), in examining and granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier filed patent.
+Added: Patent and Trademark Office (USPTO), in
+Added: examining and granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier filed patent.
In the United States, the term of a patent that covers an FDA-approved drug may also be eligible for extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process.
2 unchanged sentences
Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent applicable to an approved drug may be extended and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be extended.
−Removed: Similar provisions to extend the term of a
−Removed: patent that covers an approved drug are available in Europe and other foreign jurisdictions.
+Added: Similar provisions to extend the term of a patent that covers an approved drug are available in Europe and other foreign jurisdictions.
In the future, if and when our products receive FDA approval, we expect to apply for patent term extensions on patents covering those products.
24 unchanged sentences
Thus, we may not be able to meaningfully protect our trade secrets.
−Removed: It is our policy to require our employees, consultants, outside scientific collaborators, sponsored researchers and other advisors to execute confidentiality agreements upon the commencement of employment or consulting relationships
+Added: It is our policy to require our employees, consultants, outside scientific collaborators, sponsored researchers and other advisors to execute confidentiality agreements upon the commencement of employment or consulting relationships with us.
These agreements provide that all confidential information concerning our business or financial affairs developed or made known to the individual during the course of the individual’s relationship with us is to be kept confidential and not disclosed to third parties except in specific circumstances.
46 unchanged sentences
The FDA or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk.
−Removed: Similarly, an IRB may also require the clinical trial at the site to be halted, either temporarily or permanently (or impose other conditions), for failure to comply with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients.
+Added: Similarly, an IRB may also require the clinical trial at the site to be halted, either temporarily or permanently (or impose
+Added: other conditions), for failure to comply with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients.
In addition, some clinical trials are overseen by an independent group of qualified experts organized by the sponsor, known as a data safety monitoring board or committee.
12 unchanged sentences
In certain instances, the FDA may mandate the performance of “Phase 4” clinical trials
−Removed: Congress also recently amended the FDC Act, as part of the Consolidated Appropriations Act for 2023, in order to require sponsors of a Phase 3 clinical trial, or other “pivotal study” of a new drug or biologic to support marketing authorization, to design and submit a diversity action plan for such clinical trial.
+Added: Congress also recently amended the FDC Act to require sponsors of a Phase 3 clinical trial, or other “pivotal study” of a new drug or biologic to support marketing authorization, to design and submit a diversity action plan for such clinical trial.
The action plan must include the sponsor’s diversity goals for enrollment, as well as a rationale for the goals and a description of how the sponsor will meet them.
1 unchanged sentence
The FDA may grant a waiver for some or all of the requirements for a diversity action plan.
−Removed: It is unknown at this time how the diversity action plan may affect Phase 3 trial planning and timing or what specific information FDA will expect in such plans, but if the FDA objects to a sponsor’s diversity action plan or otherwise requires significant changes to be made, it could delay initiation of the relevant clinical trial.
+Added: If the FDA objects to a sponsor’s diversity action plan or otherwise requires significant changes to be made, it could delay initiation of the relevant clinical trial.
Concurrent with clinical trials, companies usually complete nonclinical animal studies and must also develop additional information about the chemistry and physical characteristics of the product and finalize a process for manufacturing the product in commercial quantities in accordance with current good manufacturing practices (cGMPs).
9 unchanged sentences
A waiver of such fees may be obtained under certain limited circumstances.
+Added: Congress is required to re-authorize the agency’s user fee programs every five years, and current legislative provisions supporting the prescription drug-specific program are set to expire on September 30, 2027.
The FDA has 60 days from its receipt of an NDA or BLA to determine whether the application will be filed based on the agency’s threshold determination that it is sufficiently complete to permit substantive review.
1 unchanged sentence
In this event, the NDA or BLA must be resubmitted with the additional information.
−Removed: The resubmitted application also is subject to review before the FDA
−Removed: accepts it for filing.
+Added: The resubmitted application also is subject to review before the FDA accepts it for filing.
Once the submission is filed, the FDA begins an in-depth review to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s identity, strength, quality and purity.
23 unchanged sentences
The requirement for a REMS can materially affect the potential market and profitability of the product.
−Removed: Moreover, product approval may require substantial post-approval testing and surveillance to monitor the product’s safety or efficacy.
+Added: Moreover, product approval may require substantial post-approval testing and surveillance to monitor the product’s
+Added: safety or efficacy.
Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained or problems are later identified.
Changes to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and FDA approval of a new NDA or BLA or NDA/BLA supplement before the change can be implemented.
−Removed: A supplement seeking a new indication typically requires
−Removed: clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing efficacy supplements as it does in reviewing original NDAs and BLAs.
+Added: A supplement seeking a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing efficacy supplements as it does in reviewing original NDAs and BLAs.
Disclosure of Clinical Trial Information
15 unchanged sentences
Applications submitted under the BPCA are treated as priority review applications, with all of the benefits that designation confers.
+Added: Congress periodically considers enacting new incentives or mandates applicable to pediatric drug development, and the regulatory requirements applicable to pediatric drug developers may change in the future.
+Added: For example, bipartisan legislation introduced in 2023 in the House of Representatives would have increased funding for pediatric trials;
+Added: mandated that drugs for rare diseases be studied in children;
+Added: and granted FDA authority to assess penalties against companies that do not complete required pediatric studies.
Expedited Development and Review Programs & Accelerated Approval Pathway
5 unchanged sentences
A product candidate intended to treat a serious or life-threatening disease or condition may also be eligible for breakthrough therapy designation to expedite its development and review.
−Removed: A product candidate can receive breakthrough therapy designation if preliminary clinical evidence indicates that the product candidate, alone or in combination with
−Removed: one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
+Added: A product candidate can receive breakthrough therapy designation if preliminary clinical evidence indicates that the product candidate, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
The designation includes all of the Fast Track program features, as well as more intensive FDA interaction and guidance beginning as early as Phase 1 and an organizational commitment to expedite the development and review of the product candidate, including involvement of senior managers.
11 unchanged sentences
Once an NDA or BLA is approved, a product will be subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product.
−Removed: For instance, the FDA closely regulates the post-approval marketing, labeling, advertising and promotion of drugs, including through its enforcement of standards and regulations for direct-to-consumer advertising, industry-sponsored scientific and educational activities and promotional activities involving the internet.
+Added: For instance, the FDA
+Added: closely regulates the post-approval marketing, labeling, advertising and promotion of drugs, including through its enforcement of standards and regulations for direct-to-consumer advertising, industry-sponsored scientific and educational activities and promotional activities involving the internet.
Drugs may be marketed only for the approved indications and in accordance with the provisions of the approved labeling.
−Removed: After approval, most changes to the approved product, such as adding new indications and making, certain manufacturing changes, are subject to further FDA review and approval.
Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties.
4 unchanged sentences
The FDA does, however, restrict manufacturers’ communications on the subject of off-label use of their products.
+Added: Companies may share truthful and not misleading information that is not inconsistent with the labeling, and the FDA recently published guidance for industry that outlines modernized recommendations for how drug manufacturers can share truthful, scientifically sound, and clinically relevant information on unapproved uses with health care providers in a non-promotional way.
+Added: Moreover, if there are any modifications to the product, including changes in indications, labeling or manufacturing processes or facilities, the applicant may be required to submit and obtain FDA approval of a new NDA/BLA or an NDA/BLA supplement, which may require the applicant to develop additional data or conduct additional nonclinical studies and clinical trials.
+Added: In particular, securing FDA approval for new indications is similar to the process for approval of the original indication and requires, among other things, submitting data from adequate and well-controlled clinical trials to demonstrate the product’s safety and efficacy in the new indication.
+Added: Even if such trials are conducted, the FDA may not approve any expansion of the labeled indications for use in a timely fashion, or at all.
Adverse event reporting and submission of periodic reports are required following FDA approval of an NDA or BLA.
3 unchanged sentences
Registration with the FDA subjects entities to periodic unannounced inspections by the FDA and certain state agencies to assess compliance with cGMPs and other laws and regulations.
−Removed: Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented.
Accordingly, manufacturers must continue to expend time, money and effort in the areas of production and quality-control to maintain compliance with cGMPs.
+Added: FDA regulations also require, among other things, the investigation and correction of any deviations from cGMP and the imposition of reporting and documentation requirements upon the NDA/BLA sponsor and any third-party manufacturers involved in producing the approved therapeutic product.
Regulatory authorities may withdraw product approvals or request product recalls if a company fails to comply with regulatory standards or if it encounters problems following initial marketing.
14 unchanged sentences
Both the PDMA and state laws limit the distribution of prescription pharmaceutical product samples and impose requirements to ensure accountability in distribution.
−Removed: More recently, the Drug Supply Chain Security Act (DSCSA) was enacted with the aim of building an electronic system to identify and trace certain prescription drugs distributed in the United States, including most biological products.
−Removed: The DSCSA mandates phased-in and resource-intensive obligations for manufacturers, wholesale distributors and dispensers over a 10-year period that culminated in November 2023.
+Added: The Drug Supply Chain Security Act (DSCSA) was enacted in 2013 with the aim of building an electronic system to identify and trace certain prescription drugs distributed in the United States, including most biological products.
+Added: The DSCSA mandated resource-intensive obligations for manufacturers, wholesale distributors and dispensers over a 10-year period that culminated in November 2023.
+Added: Most recently, the FDA announced a one-year stabilization period to November 2024 followed by trading partner-specific exemptions through specified dates in 2025, giving entities subject to the DSCSA additional time to finalize interoperable tracking systems and to ensure supply chain continuity.
From time to time, new legislation and regulations may be implemented that could significantly change the statutory provisions governing the approval, manufacturing and marketing of products regulated by the FDA.
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However, according to the guidance, if a diagnostic device and a drug are to be studied together to support their respective approvals, both products can be studied in the same investigational study, if the study meets both the requirements of applicable IDE regulations and the IND regulations.
−Removed: The guidance provides that, depending on the details of the study plan and degree of risk posed to subjects, a sponsor may seek to submit an IND alone, or both an IND and an IDE.
+Added: The guidance provides that, depending on the
+Added: details of the study plan and degree of risk posed to subjects, a sponsor may seek to submit an IND alone, or both an IND and an IDE.
The FDA has generally required companion diagnostics intended to select the patients who will respond to cancer treatment to obtain approval of a PMA for that diagnostic simultaneously with approval of the therapeutic.
4 unchanged sentences
As part of the PMA review, the FDA will typically inspect the manufacturer’s facilities for compliance with the Quality System Regulation (QSR), which imposes elaborate testing, control, documentation and other quality assurance requirements.
+Added: The QSR is being replaced by a new final rule called the Quality Management System Regulation (QMSR), which is aimed at harmonizing the FDA’s medical device current good manufacturing practice regulations with the International Organization for Standardization standard for device quality management systems (ISO 13485:2016).
+Added: The effective date for the QMSR final rule is February 2, 2026.
+Added: Until then, device manufacturers are required to comply with the QSR.
If the FDA’s evaluation of the PMA application is favorable, the FDA may issue an approvable letter requiring the applicant’s agreement to specific conditions, such as changes in labeling, or specific additional information, such as submission of final labeling, in order to secure final approval of the PMA.
4 unchanged sentences
The PMA can include post-approval conditions that the FDA believes necessary to ensure the safety and effectiveness of the device, including, among other things, restrictions on labeling, promotion, sale and distribution.
−Removed: Once granted, PMA
−Removed: approval may be withdrawn by the FDA if compliance with post approval requirements, conditions of approval or other regulatory standards are not maintained or problems are identified following initial marketing.
+Added: Once granted, PMA approval may be withdrawn by the FDA if compliance with post approval requirements, conditions of approval or other regulatory standards are not maintained or problems are identified following initial marketing.
After a device is commercialized, it remains subject to significant regulatory requirements.
10 unchanged sentences
An ANDA provides for marketing of a drug product that has the same active ingredients in the same strengths and dosage form as the listed drug and has been shown through bioequivalence testing to be therapeutically equivalent to the listed drug.
−Removed: Other than the requirement for bioequivalence testing, ANDA applicants are not required to conduct, or submit results of, nonclinical or clinical tests to prove the safety or effectiveness of their drug product.
+Added: Other than the requirement for bioequivalence testing, ANDA
+Added: applicants are not required to conduct, or submit results of, nonclinical or clinical tests to prove the safety or effectiveness of their drug product.
Drugs approved in this way are commonly referred to as “generic equivalents” to the listed drug and can often be substituted by pharmacists under prescriptions written for the original listed drug pursuant to each state’s laws on drug substitution.
11 unchanged sentences
The ANDA application also will not be approved until any applicable non-patent exclusivity listed in the Orange Book for the referenced product has expired.
−Removed: Market exclusivity provisions under the FDC Act can delay the submission or the approval of certain marketing applications.
−Removed: Upon NDA approval of a new chemical entity (NCE), which is a drug that contains no active moiety (which is the molecule or ion responsible for the action of the drug substance) that has been approved by FDA in any other NDA, that drug receives five years of non-patent data exclusivity within the United States during which FDA cannot accept for review any ANDA seeking approval of a generic version of that drug, or an NDA submitted under
−Removed: Section 505(b)(2) (505(b)(2) NDA) submitted by another company for another drug based on the same active moiety, regardless of whether the drug is intended for the same indication as the original innovative drug or for another indication, where the applicant does not own or have a legal right of reference to all the data required for approval.
−Removed: An application may be submitted one year before NCE exclusivity expires if a Paragraph IV certification is filed, i.e., certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder.
−Removed: If there is no listed patent in the Orange Book, there may not be a Paragraph IV certification, and, thus, no application may be filed before the expiration of the exclusivity period.
−Removed: Certain changes to a drug, such as the addition of a new indication to the package insert, or new dosages or strengths of an existing drug, can be the subject of a three-year non-patent period of marketing exclusivity if the NDA (or supplement to an existing NDA) contains reports of new clinical investigations (other than bioavailability studies) conducted or sponsored by the applicant that are deemed by the FDA to be essential to the approval of the application.
+Added: Regulatory exclusivity provisions under the FDC Act can delay the submission or the approval of certain marketing applications for small-molecule drug products.
+Added: Upon NDA approval of a new chemical entity (NCE), which is a drug that contains no active moiety (which is the molecule or ion responsible for the action of the drug substance) that has been approved by FDA in any other NDA, that NDA receives five years of non-patent data and marketing exclusivity within the United States during which FDA cannot accept for review any (i) ANDA seeking approval of a generic version of that drug, or (ii) any NDA submitted under Section 505(b)(2) (505(b)(2) NDA) of the Act (also referred to as a submitted by another company for another drug based on the same active moiety, regardless of whether the drug is intended for the same indication as the original innovative drug or for another indication, where the applicant does not own or have a legal right of reference to all the data required for approval.
+Added: An application referencing the protected NDA may be submitted one year before NCE exclusivity expires if a Paragraph IV certification is filed, i.e., certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder.
+Added: If there is no listed patent in the Orange Book, there may not be a Paragraph IV certification, and, thus, no application may be filed before the expiration of the five-year exclusivity period.
+Added: Certain changes to a drug, such as the addition of a new indication to the package insert, or new dosages or strengths of an existing drug, can be the subject of a three-year non-patent period of data exclusivity if the NDA (or supplement to an existing NDA) contains reports of new clinical investigations (other than bioavailability studies) conducted or sponsored by the applicant that are deemed by the FDA to be essential to the approval of the application.
This three-year exclusivity covers only the modification for which the drug received approval on the basis of the new clinical investigations and does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for drugs containing the active agent for the original indication or condition of use.
−Removed: Five-year and three-year exclusivity will not delay the submission or approval of a full NDA.
+Added: Five-year and three-year exclusivity will not delay the submission or approval of a full NDA that is does not reference data in another drug’s approved application.
However, an applicant submitting a full NDA would be required to conduct, or obtain a right of reference to, all of the nonclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.
16 unchanged sentences
If pediatric studies are performed and accepted by the FDA as responsive to a written request from FDA, as described above, the 12-year exclusivity period will be extended for an additional six months.
−Removed: addition, the FDA will not accept an application for a biosimilar or interchangeable product based on the reference biological product until four years after the date of first licensure of the reference product.
+Added: In addition, the FDA will not accept an application for a biosimilar or interchangeable product based on the reference biological product until four years after the date of first licensure of the reference product.
“First licensure” typically means the initial date the particular product at issue was licensed in the United States.
3 unchanged sentences
The BPCIA is complex and continues to be interpreted and implemented by the FDA.
−Removed: In addition, recent government proposals have sought to reduce the 12-year reference product exclusivity period.
+Added: In addition, policy proposals have sought to reduce the 12-year reference product exclusivity period and, more recently, to potentially eliminate the separate statutory definition of an interchangeable biological product.
As a result, the ultimate impact, implementation and meaning of the BPCIA continue to be subject to uncertainty.
20 unchanged sentences
This led to significant variations in the member state regimes.
−Removed: Under the previous regime, before a clinical trial could be initiated, a clinical trial application
−Removed: must have been approved in each of the EU countries where the trial was to be conducted by two distinct bodies:
+Added: Under the previous regime, before a clinical trial could be initiated, a clinical trial application must have been approved in each of the EU countries where the trial was to be conducted by two distinct bodies:
the National Competent Authority (NCA) and one or more Ethics Committees (ECs).
4 unchanged sentences
The extent to which ongoing clinical trials are governed by the Clinical Trials Regulation depends on when the Clinical Trials Regulation became applicable and on the duration of the individual clinical trial.
−Removed: If a clinical trial continues for more than three years from the day on which the Clinical Trials Regulation became applicable the Clinical Trials Regulation will at that time begin to apply to the clinical trial.
+Added: If a clinical trial continues for more than three years from the day on which the Clinical Trials Regulation became applicable the Clinical Trials Regulation will at that time begin to apply to
+Added: the clinical trial.
In addition, use of the new EU-wide application procedure being implemented via the Clinical Trial Information System, became mandatory for new clinical trial application submissions as of February 1, 2023.
13 unchanged sentences
Upon receiving an MA, reference product candidates generally receive eight years of data exclusivity and an additional two years of market exclusivity.
−Removed: If granted, the data exclusivity period prevents generic applicants from relying on the nonclinical and clinical trial data contained in the dossier of the reference product when applying for a generic MA in the
−Removed: EU during a period of eight years from the date on which the reference product was first authorized in the EU.
+Added: If granted, the data exclusivity period prevents generic applicants from relying on the nonclinical and clinical trial data contained in the dossier of the reference product when applying for a generic MA in the EU during a period of eight years from the date on which the reference product was first authorized in the EU.
The market exclusivity period prevents a successful generic applicant from commercializing its product in the EU until 10 years have elapsed from the initial MA of the reference product in the EU.
2 unchanged sentences
In April 2023, the European Commission proposed widespread changes to the existing pharmaceutical legislation that would, among other things, alter the data exclusivity periods available to MA holders.
−Removed: The proposed reforms must be reviewed and approval by the EU Parliament and Council, and in light of their controversial nature it is unclear whether they will be adopted as proposed or further revised.
+Added: The proposed reforms must be reviewed and approval by the European Parliament and Council, as well as EU Member States, and in light of their controversial nature it is unclear whether they will be adopted as proposed or further revised.
EU Post-Approval Requirements
11 unchanged sentences
Brexit and the Regulatory Framework in the United Kingdom (UK)
−Removed: The UK formally withdrew from the EU on January 31, 2020 (known as Brexit), following which the UK and EU entered into a trade agreement known as the Trade and Cooperation Agreement (TCA), which went into effect on January 1, 2021.
−Removed: The TCA includes specific provisions concerning pharmaceuticals, which include the mutual recognition of GMP inspections of manufacturing facilities for medicinal products and GMP documents issued, but does not foresee wholesale mutual recognition of UK and EU pharmaceutical regulations.
−Removed: As a result of Brexit, UK licensing decisions were transferred from EMA to the Medicines and Healthcare Products Regulatory Agency (MHRA) the UK Regulatory Body.
−Removed: For a period of two years following January 1, 2021, the UK will continue to adopt decisions taken by the European Commission on the approval of new marketing authorizations.
−Removed: However, companies will be required to submit an identical application to the MHRA upon the CHMP positive opinion of the application.
−Removed: The MHRA will then wait for the European Commission decision on approval.
−Removed: Since the regulatory framework in the United Kingdom covering the quality, safety and efficacy of pharmaceutical products, clinical trials, marketing authorization, commercial sales and distribution of pharmaceutical products is derived
−Removed: from European Union directives and regulations, Brexit could materially impact the future regulatory regime as it applies to medicinal products and the approval of product candidates in the United Kingdom.
+Added: The UK formally withdrew from the EU on January 31, 2020 (known as Brexit), following which the UK licensing decisions were transferred from the EMA to the Medicines and Healthcare Products Regulatory Agency (MHRA) the UK’s regulatory body.
+Added: Between January 1, 2021 and January 2023, the UK continued to adopt decisions taken by the European Commission on the approval of new marketing authorizations, although companies were required to submit an identical application to the MHRA upon the CHMP positive opinion of the application and the MHRA followed the European Commission decision on approval.
+Added: In March 2023, the UK government and the European Commission reached agreement on a regulatory framework, referred to as the Windsor Framework.
+Added: The Windsor Framework will apply as of January 1, 2025 and changes the existing system for the regulation of pharmaceutical products in the UK.
+Added: Specifically, the MHRA will be responsible for approving all medicines intended to be marketed in the United Kingdom, while the EMA will no longer be involved in approving medicines intended for sale in Northern Ireland.
Other Healthcare Laws
5 unchanged sentences
Violations of this law are punishable by imprisonment, criminal fines, administrative civil money penalties and exclusion from participation in federal healthcare programs.
−Removed: In addition, the Patient Protection and Affordable Care Act (discussed further below), among other things, amended the intent requirement of the federal Anti-Kickback Statute and two of the five criminal healthcare fraud statutes created by the Health Insurance Portability and Accountability Act of 1996 (HIPAA).
+Added: In addition, the
+Added: Patient Protection and Affordable Care Act (discussed further below), among other things, amended the intent requirement of the federal Anti-Kickback Statute and two of the five criminal healthcare fraud statutes created by the Health Insurance Portability and Accountability Act of 1996 (HIPAA).
A person or entity no longer needs to have actual knowledge of these two provisions in the statute or specific intent to violate them;
12 unchanged sentences
Also, many states have similar fraud and abuse statutes or regulations that apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.
−Removed: Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines, or the relevant compliance guidance promulgated by the federal government, in addition to requiring drug manufacturers to report information related to payments to physicians and other health care providers or
−Removed: marketing expenditures to the extent that those laws impose requirements that are more stringent than the Physician Payments Sunshine Act.
+Added: Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines, or the relevant compliance guidance promulgated by the federal government, in addition to requiring drug manufacturers to report information related to payments to physicians and other health care providers or marketing expenditures to the extent that those laws impose requirements that are more stringent than the Physician Payments Sunshine Act.
Efforts to ensure that business arrangements with third parties comply with applicable state, federal and foreign healthcare laws and regulations involve substantial costs.
3 unchanged sentences
Healthcare Reform and Potential Changes to Healthcare Laws
−Removed: In the United States and some foreign jurisdictions, there have been, and continue to be, several legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of therapeutic product candidates, restrict or regulate post-approval activities, and affect the ability to profitably sell therapeutic product candidates that obtain marketing approval.
+Added: In the United States and some foreign jurisdictions, there have been, and continue to be, several legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of therapeutic product candidates, restrict or regulate post-approval activities, and affect the ability to profitably
+Added: sell therapeutic product candidates that obtain marketing approval.
The FDA’s and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or delay marketing approval of our product candidates.
11 unchanged sentences
This calculation is made on a drug product by drug product basis and the amount of the rebate owed to the federal government is directly dependent on the volume of a drug product that is paid for by Medicare Parts B or D.
−Removed: Additionally, starting for payment year 2026, CMS will negotiate drug prices annually for a select number of single
−Removed: source Part D drugs without generic competition.
+Added: Additionally, starting for payment year 2026, CMS is negotiating drug prices annually for a select number of single source Part D drugs without generic competition.
CMS will also negotiate drug prices for a select number of Part B drugs starting for payment year 2028.
If a product is selected by CMS for negotiation, it is expected that the revenue generated from such product will decrease.
−Removed: CMS has begun to implement these new authorities, including with its publication of the first list of 10 Medicare Part D drugs for negotiation in September 2023 and entering into an agreement to conduct negotiations with the relevant manufacturers of those selected drugs in October 2023.
+Added: CMS has begun to implement these new authorities entering into a first set of agreements with pharmaceutical manufacturers to conduct price negotiations in October 2023 and ultimately announcing the first round of negotiated prices for the first 10 drugs in August 2024;
+Added: those negotiated “maximum fair prices” will be effective as of January 1, 2026 (payment year 2026).
+Added: CMS is currently initiating activities for the second year of the program and published the next 15 drugs selected for negotiation in January 2025.
However, their impact on the biopharmaceutical industry in the United States remains uncertain, in part because multiple large pharmaceutical companies and other stakeholders (e.g., the U.S.
Chamber of Commerce) have initiated federal lawsuits against CMS arguing the program is unconstitutional for a variety of reasons, among other complaints.
+Added: The outcome of such ongoing lawsuits, as well as potential legislative changes enacted by Congress or programmatic changes implemented at CMS by the Trump Administration, may impact the IRA drug price negotiation program in the future.
Individual states in the United States have also increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
In December 2020, the U.S.
−Removed: Supreme Court held unanimously that federal law does not preempt the states’ ability to regulate pharmacy benefit managers (PBMs) and other members of the health care and pharmaceutical supply chain, an important decision has led to further and more aggressive efforts by states in this area.
−Removed: The FTC in mid-2022 also launched sweeping investigations into the practices of the PBM industry that could lead to additional federal and state legislative or regulatory proposals targeting such entities’ operations, pharmacy networks, or financial arrangements, and Congress has been actively convening hearings and considering legislation related to PBM practices.
+Added: Supreme Court held unanimously that federal law does not preempt the states’ ability to regulate pharmacy benefit managers (PBMs) and other members of the health care and pharmaceutical supply chain, an important decision that has led to
+Added: further and more aggressive efforts by states in this area.
+Added: The FTC in mid- 2022 also launched sweeping investigations into the practices of the PBM industry, and published interim reports with its findings in mid-2024 and January 2025, that could lead to additional federal and state legislative or regulatory proposals targeting such entities’ operations, pharmacy networks, or financial arrangements, including in the current 2025-2026 congressional session where PBM reform continues to be a bipartisan priority.
+Added: During the previous congressional session, numerous PBM reforms were considered in both the Senate and the House of Representatives;
+Added: they included diverse legislative proposals such as eliminating rebates;
+Added: divorcing service fees from the price of a drug, discount, or rebate;
+Added: prohibiting spread pricing;
+Added: limiting administrative fees;
+Added: requiring PBMs to report formulary placement rationale;
+Added: promoting transparency.
Significant efforts to change the PBM industry as it currently exists in the U.S.
16 unchanged sentences
If these third-party payors do not consider our products to be cost-effective compared to other therapies, they may not cover our products after approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow us to sell our products on a profitable basis.
−Removed: companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or biological products.
+Added: In addition, companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or biological products.
Moreover, in some foreign countries, the proposed pricing for a therapeutic product must be approved before it may be lawfully marketed.
3 unchanged sentences
There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our therapeutic candidates, if approved.
−Removed: Historically, therapeutic candidates launched in the European Union do not follow price structures of the United States and generally tend to be significantly lower.
+Added: Historically,
+Added: therapeutic candidates launched in the European Union do not follow price structures of the United States and generally tend to be significantly lower.
Foreign Corrupt Practices Act
7 unchanged sentences
The SEC is involved with the books and records.
+Added: In February 2025, President Trump issued an executive order directing the DOJ to pause enforcement of the FCPA and to issue new enforcement guidelines that take into consideration U.S.
+Added: national security and the competitiveness of U.S.
+Added: companies abroad.
+Added: It is unclear how this presidential directive may affect the biopharmaceutical industry as a whole or our business in particular.
Employees and Human Capital Resources
As of December 31, 2024, we had 52 employees, all of whom were full-time and 36 of whom were engaged in research and development activities.
−Removed: Twenty-two of our employees hold Ph.D.
−Removed: Nearly all of our R&D personnel and our administrative team are based in and around Burlingame, CA and Rockville, MD.
+Added: Twenty-three of our employees hold Ph.D.
None of our employees are represented by a labor union or covered under a collective bargaining agreement.
18 unchanged sentences
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.