On May 13, 2024 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, reported corporate updates, and announced financial results for the quarter ended March 31, 2024 (Press release, Allogene, MAY 13, 2024, View Source [SID1234643128]).

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"We are very proud of the progress we’ve made across our portfolio, in particular the transformative potential of our pivotal ALPHA3 trial with cema-cel which is expected to readout in 2026. Securing the EU and UK rights reinforces our conviction in the cema-cel program," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "We will continue to focus all of our resources on advancing these core programs and believe we are well-positioned to change the CAR T treatment landscape for the benefit of patients."

Key Corporate Updates

Expansion of CD19 Oncology Program Rights
The Company has obtained development and commercialization oncology rights to all EU Member States and the United Kingdom (Extended Territory) for its CD19-directed allogeneic cell therapy products from Servier.

These new expanded rights, combined with the U.S. rights already owned by the Company, substantially increase the potential total market opportunity from more than $6 billion in the U.S. alone to more than $9.5 billion in the combined U.S. and Extended Territory. It is expected that the future multibillion-dollar revenue potential for cema-cel now could increase by 50% with these expanded rights. The Company also has the ability to obtain the development and commercialization rights for cema-cel in Japan and China in the future at no additional cost, subject to Allogene demonstrating the resources to pursue those markets.

Program Updates

Cema-Cel: Pivotal Phase 2 ALPHA3 1L Consolidation Trial in Large B Cell Lymphoma (LBCL)
The Company continues to focus on the development of its investigational product cemacabtagene ansegedleucel, or cema-cel (previously known as ALLO-501A), as part of the first line (1L) treatment plan for LBCL patients who are at risk of relapse following 1L chemoimmunotherapy. The ALPHA3 trial will be conducted in a wide array of cancer treatment centers, including community cancer centers where most earlier line patients seek care.

This innovative trial will identify patients at high risk for relapse after 1L treatment by utilizing a novel and highly accurate test for minimal residual disease, or MRD. This investigational test is being developed by our partners Foresight Diagnostics and aims to offers improved prediction over existing methods for future relapse after completion of 1L treatment. ALPHA3 takes advantage of the allogeneic attributes of cema-cel. With off-the-shelf availability and convenience, cema-cel will be administered as a one-time infusion immediately upon detection of MRD at the completion of six cycles of R-CHOP or other standard 1L chemoimmunotherapy regimen. The outcome of this consolidation treatment could potentially improve the cure rate and uniquely position cema-cel to become the standard "7th cycle" of frontline treatment available to all eligible patients with MRD.

Start-up activities for the ALPHA3 trial are ongoing with a planned study initiation in mid-2024. This randomized study will enroll approximately 240 patients and is designed to demonstrate a meaningful improvement in event free survival (EFS) in patients treated with cema-cel relative to patients who receive the current standard of care (observation). Efficacy analyses are expected to occur in 2026 and will include the Independent Data Safety Monitoring Board (IDSMB) interim EFS analysis in 1H 2026 and the data readout of the primary EFS analysis in 2H 2026 with a Biologics License Application (BLA) submission targeted for 2027.

Cema-Cel: Phase 1 Trial in Chronic Lymphocytic Leukemia (CLL)
Enrollment is ongoing in the relapsed/refractory (r/r) CLL cohort of the Phase 1 ALPHA2 trial of cema-cel. While recent approval of an autologous CD19 CAR T therapy has been a positive step for patients with r/r CLL T cell dysfunction, and high circulating leukemia burden often found in patients with CLL make the isolation of functional T cells for autologous CAR T manufacturing difficult. This trial has been driven by investigator enthusiasm for an allogeneic CAR T to potentially boost the curative power of CAR T.

Initial data readout from the Phase 1 ALPHA2 CLL cohort (n=12) is projected by year-end 2024 with a Phase 2 pivotal study expected in 2025.

ALLO-329: CD19/CD70 Dual CAR with Dagger Technology in Autoimmune Disease (AID)
The Company has applied its deep understanding of CAR T research and development to design next-generation allogeneic CAR T investigational products that could sustain the scale of the AID market while also meeting the unique requirements for these patients.

ALLO-329, the Company’s CRISPR-based AlloCAR T investigational product for AID, incorporates the Dagger technology which is intended to eliminate the need for lymphodepletion while targeting CD19+ B-cells and CD70+ activated T-cells, both of which are likely to play a role in AID.

The Company plans to file an Investigational New Drug (IND) application in Q1 2025 and expects to have proof-of-concept by YE 2025.

ALLO-316: TRAVERSE Trial in Renal Cell Carcinoma (RCC)
In April 2024, the Company announced a $15 million grant from the California Institute for Regenerative Medicine (CIRM) to support the ongoing TRAVERSE trial with ALLO-316 in RCC.

The Company has developed and implemented a diagnostic and treatment algorithm in the TRAVERSE trial that may mitigate the treatment-associated hyperinflammatory response without compromising the CAR T function needed to eradicate solid tumors. This builds upon the field’s understanding of how certain drugs can act as a "safety key" to mitigate hyperinflammatory response without compromising CAR T function or efficacy.

Details on this potentially cornerstone discovery in the Phase 1 TRAVERSE trial are planned for release Q2 2024. A Phase 1 data update from approximately 20 patients with CD70 positive RCC is planned by YE 2024.

2024 First Quarter Financial Results
•Research and development expenses were $52.3 million for the first quarter of 2024, which includes $3.8 million of non-cash stock-based compensation expense.
•General and administrative expenses were $17.3 million for the first quarter of 2024, which includes $8.1 million of non-cash stock-based compensation expense.
•Net loss for the first quarter of 2024 was $65.0 million, or $0.38 per share, including non-cash stock-based compensation expense of $11.9 million.
•The Company had $397.3 million in cash, cash equivalents, and investments as of March 31, 2024.

Based on the cash runway as of March 31, 2024, the Company expects its cash runway to fund operations into 2026. The Company expects a decrease in cash, cash equivalents, and investments of approximately $200 million in 2024. GAAP

Operating Expenses are expected to be approximately $300 million, including estimated non-cash stock-based compensation expense of approximately $60 million. These estimates exclude any impact from potential business development activities.

Conference Call and Webcast Details
Allogene will host a live conference call and webcast today at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time to discuss financial results and provide a business update. If you would like the option to ask a question on the conference call, please use this link to register. Upon registering for the conference call, you will receive a personal PIN to access the call, which will identify you as the participant and allow you the option to ask a question. The listen-only webcast will be made available on the Company’s website at www.allogene.com under the Investors tab in the News and Events section. Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.

About Cemacabtagene Ansegedleucel (Previously Known as ALLO-501A) Cemacabtagene ansegedleucel, or cema-cel is a next generation anti-CD19 AlloCAR T investigational product for the treatment of large B cell lymphoma (LBCL). The ALPHA3 pivotal Phase 2 trial in first line (1L) consolidation for the treatment of LBCL is expected to begin mid-2024. In June 2022, the U.S. Food and Drug Administration granted Regenerative Medicine Advanced Therapy (RMAT) designation to cema-cel in third line (3L) r/r LBCL.

On May 13, 2024 Akoya Biosciences, Inc. (Nasdaq: AKYA) ("Akoya"), The Spatial Biology Company, reported its financial results for the first quarter ending March 31, 2024 (Press release, Akoya Biosciences, MAY 13, 2024, View Source [SID1234643127]).

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Business Highlights

● Revenue was $18.4 million in the first quarter of 2024, compared to $21.4 million in the prior year period; a decrease of 14%. Reagents and services revenue continued to increase.
● Akoya announced the establishment of a new Manufacturing Center of Excellence in Marlborough, Massachusetts to scale internal reagent manufacturing to meet the accelerating demand for reagents.
● Akoya’s partner Acrivon Therapeutics presented initial positive Phase 2b clinical data for the ACR-368 therapeutic in patients positive for the ACR-368 OncoSignature Assay in ovarian and endometrial cancer, deployed on the PhenoImager HT platform.
● Akoya and NeraCare, a leading developer of laboratory tests for the prognosis of melanoma patients, announced an exclusive partnership to enable personalized therapy selection for early-stage melanoma patients at high risk of relapse and death.
● Akoya and Shanghai KR Pharmtech announced that the KR-HT5 instrument, based on the PhenoImager HT, has received premarket approval from China’s National Medical Products Administration (NMPA).

"While we made meaningful progress in advancing both our operational and clinical objectives, our first quarter results fell short of expectations due to three main factors. First, systemic pressure on capital expenditures persisted. Second, certain pharmaceutical partner lab services revenue were deferred to the second half of 2024 due to revised clinical trial milestones. Third, the completion and launch of our fully operational Manufacturing Center of Excellence temporarily impacted reagent fulfillment times, delaying instrument purchases," said Brian McKelligon, CEO of Akoya Biosciences. "With the industry’s leading installed base, normalization of pharmaceutical partner revenue in the second half of 2024, and now resolved reagent availability issues, we believe that our foundational initiatives will lead us back to strong top-line growth and achievement of our profitability objectives."

First Quarter 2024 Financial Results

● Revenue was $18.4 million in the first quarter of 2024, compared to $21.4 million in the prior year period; a decrease of 14%. Reagents and services revenue continued to increase.
● For the first quarter of 2024, reported gross margin was 46% while non-GAAP adjusted gross margin was 57% when excluding the write off from discontinued legacy instruments. Both GAAP and non-GAAP adjusted gross margin were 57% for the first quarter of 2023.
● For the first quarter of 2024, operating expenses were $30.0 million and non-GAAP operating expenses were $25.6 million when excluding an impairment charge for facility consolidation and restructuring associated with a reduction in force in January. Both GAAP and non-GAAP operating expenses were $29.7 million for the first quarter of 2023.
● For the first quarter of 2024, loss from operations was $21.6 million and non-GAAP loss from operations was $15.2 million, excluding the items noted above. Both GAAP and non-GAAP loss from operations were $17.4 million for the first quarter of 2023.
● Ended the quarter with an instrument installed base of 1,213 (354 PhenoCyclers, 859 PhenoImagers), a year-over-year increase of 22% compared to an installed base of 992 in the prior year period (273 PhenoCyclers, 719 PhenoImagers).
● 1,307 total publications citing Akoya’s technology as of March 31, 2024, compared to 860 total publications in the prior year period: an increase of 52%.
● $61.6 million of cash, cash equivalents and marketable securities as of March 31, 2024.

2024 Financial Outlook

Akoya is updating its revenue outlook for the full year 2024 while maintaining its commitment to achieving operating cash flow breakeven by year end. The Company now expects full year 2024 revenue to be in the range of $104.0-$112.0 million.

Webcast and Conference Call Details

Akoya will host a conference call today, May 13, 2024, at 5:00 p.m. Eastern Time to discuss its first quarter 2024 financial results. Investors interested in listening to the conference call are required to register online. A live webcast of the conference call will be available on the "Investors" section of the Company’s website at View Source The webcast will be archived on the website following the completion of the call for three months.

On May 13, 2024 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, reported that five abstracts have been accepted for presentation at the 2024 Society of Nuclear Medicine & Molecular Imaging (SNMMI) Annual Meeting being held June 8 – 11, 2024, in Toronto, Canada (Press release, Actinium Pharmaceuticals, MAY 13, 2024, View Source [SID1234643126]). The abstracts will feature results from the Phase 3 SIERRA trial of Iomab-B, a CD45 targeting ARC with the Iodine-131 payload, intended for conditioning to prepare patients for a potentially curative bone marrow transplant (BMT) and results from a Phase 1b trial of Actimab-A, a CD33 targeting ARC with the Actinium-225 payload, in combination with the chemotherapy regimen CLAG-M. Iomab-B and Actimab-A are the only targeted radiotherapies in development for patients with relapsed/refractory acute myeloid leukemia (r/r AML), a blood cancer that is highly sensitive to radiation. In addition, an abstract detailing proprietary linker technology applicable for solid tumor targeting ARCs developed by Actinium will be presented for the first time.

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Sandesh Seth, Actinium’s Chairman and CEO, said, "Our presence at this year’s SNMMI showcases the breadth of Actinium’s capabilities and leadership in the development of Antibody Radiation Conjugates. We look forward to highlighting the potential for targeted radiotherapy in blood cancers to the nuclear medicine community, which represents a significant expansion opportunity for the field. The data from Iomab-B and Actimab-A that will be presented at SNMMI demonstrate the potential of targeted radiation to treat patients with high-risk, difficult-to-treat r/r AML, including the ability overcome mutations such as TP53 and those who have had extensive prior therapies."

Actinium’s SNMMI presentations are detailed below:

Safety and Dosimetric Analysis of Lintuzumab-Ac225 in Combination with Intensive CLAG-M Chemotherapy in Patients with Relapsed/Refractory AML

Exploratory Analysis of Bone Marrow Dosimetry from the Randomized Phase 3 SIERRA Trial of Iomab-B (131I-apamistamab) Prior to HCT in Relapsed/Refractory Acute Myeloid Leukemia

Survival Outcomes and Dosimetric Analysis of Iomab-B (131I-apamistamab) Followed by Allogeneic Hematopoietic Cell Transplant for Patients with TP53 Mutated Relapsed/Refractory AML

Mathematical Modeling of Exposure Measurements Following High-Dose Targeted Therapy Using 131I-apamistamab: Analysis From the Large Multicenter Phase III SIERRA Trial

Evaluation of novel DOTA-based linkers for improved targeted radiotherapy delivery to solid tumors

About the SNMMI Annual Meeting

The SNMMI Annual Meeting is recognized as the premier educational, scientific, research, and networking event in nuclear medicine and molecular imaging. The four-day event, taking place each June, provides physicians, technologists, pharmacists, laboratory professionals, and scientists with an in-depth view of the latest research and development in the field as well as providing insights into practical applications for the clinic.

On May 13, 2024 Barinthus Biotherapeutics plc (NASDAQ: BRNS), a clinical-stage biopharmaceutical company developing novel T cell immunotherapeutic candidates designed to guide the immune system to overcome chronic infectious diseases, autoimmunity, and cancer, reported its financial results for the first quarter of 2024 and provided an overview of the Company’s progress (Press release, Barinthus Biotherapeutics, MAY 13, 2024, View Source [SID1234643119]).

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"So far in 2024 we have continued to make strides across our programs. Notably, we received clearance from the FDA on an IND to progress VTP-1000 in a first in human clinical trial in celiac disease, as well as clearance from the Australian Ethics Committee on this trial. We expect to begin our Phase 1 trial of VTP-1000 in participants with celiac disease in the coming months. Additionally, we reported topline final data from the Phase 1b/2 trial of VTP-200 in participants with persistent high-risk (hr) human papillomavirus (HPV) infections," said Bill Enright, Chief Executive Officer of Barinthus Bio. "Looking ahead to Q2, we will present additional interim data from our VTP-300 hepatitis B trials at the European Association for the Study of the Liver (EASL) Congress in June. This follows the encouraging data presented at The American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting in November last year.

We will also welcome Dr. Leon Hooftman as our new Chief Medical Officer in June and look forward to him supporting the growth of our robust pipeline and programs."
Recent Corporate Developments
Clinical developments
•VTP-1000 (Celiac Disease): In April 2024, we received clearance from the U.S. FDA on an Investigational New Drug (IND) application, as well as from the Australian regulatory authorities, to progress VTP-1000 in a first in human clinical trial in celiac disease. GLU001 is a randomized, placebo-controlled Phase 1 trial with a controlled gluten challenge to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VTP-1000 in adults with celiac disease. The study is designed in two parts; a single ascending dose part followed by a multiple ascending dose part, each randomized and placebo-controlled with three dose levels. The primary endpoint is assessment of the safety and tolerability of single and multiple dosing, and determination of a dose and schedule for further investigation. The trial also aims to demonstrate proof-of-principle of induction of immune tolerance and early proof-of-concept for VTP-1000, as a potential treatment for celiac disease, based on assessment of pharmacodynamics and preliminary efficacy determined by means of a controlled gluten challenge.

•VTP-200 (HPV): In April 2024, we announced topline final data from the APOLLO trial, (also known as HPV001) a Phase 1b/2 dose-ranging study of VTP-200 in women with low-grade cervical lesions associated with persistent hrHPV infection. The APOLLO study met its primary safety endpoint, demonstrating that VTP-200 was generally well-tolerated and was administered with no treatment-related grade 3 or higher unsolicited adverse events (AEs) and no treatment-related serious AEs. Positive trends in clearance rate for both hrHPV (60%, Group 2) and cervical lesions (67%, Groups 2 and 5), were observed in the groups receiving the highest ChAdOx dose. Pooled data from the five different active dose groups demonstrated no statistically significant improvement in either hrHPV or cervical lesion clearance in comparison to the placebo group.
•VTP-300 (HBV): In April 2024, abstracts on interim data from HBV003 and AB-729-202 were accepted for presentation at the upcoming EASL Congress in Milan, Italy, June 5-8, 2024.

Management Team

•On May 1, 2024, we announced the appointment of Dr. Leon Hooftman as Chief Medical Officer. Dr. Hooftman will join the company on June 3, 2024, and brings significant drug development expertise across a broad array of therapeutic areas including immunology, autoimmunity, hematology, oncology and infectious diseases.

Upcoming Milestones
•In the second quarter of 2024, the Company expects to:
◦VTP-300 (HBV): Present interim data from HBV003, our Phase 2b trial evaluating additional dosing of VTP-300 and timing of PD-1 inhibition, in participants with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NUC) therapy at the EASL Congress in June.
◦VTP-300 (HBV): Announce interim data from the Phase 2a AB-729-202 clinical trial evaluating the combination of VTP-300 and Arbutus’ imdusiran, in participants with CHB on NUC therapy following presentation at the EASL Congress in June.
•In the third quarter of 2024, the Company expects to:
◦VTP-1000 (Celiac Disease): Dose the first patient in GLU001, a randomized, placebo-controlled Phase 1 trial with a controlled gluten challenge to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VTP-1000 in adults with celiac disease. This timing update is based on the latest feasibility and expected site set-up timelines.
First Quarter 2024 Financial Highlights
•Cash position: As of March 31, 2024, cash, cash equivalents and restricted cash was $130.0 million, compared to $142.1 million as of December 31, 2023. The cash used in operating activities was $11.8 million in the first quarter of 2024, primarily resulting from development of our pipeline and ongoing clinical trials. Based on current research and development plans, the Company expects its cash runway to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2025.
•Revenue: Revenue was nil in the first quarter of 2024 compared to $0.5 million in the first quarter of 2023 and was due to no commercial sales of Vaxzevria by AstraZeneca in 2024.
•Research and development expenses: Research and development expenses were $11.1 million in the first quarter of 2024 compared to $9.8 million in the first quarter of 2023, with the increase mainly attributable to hiring of personnel and increased costs related to the advancement of our programs. The quarter-on-quarter R&D expense per program is outlined in the following table.

Year ended Three months ended March 31, 2024 Three months ended March 31, 2023 Change
$000 $000 $000
Direct research and development expenses by program:
VTP-200 HPV $ 1,253 $ 1,338 $ (85)
VTP-300 HBV 1,913 2,118 (205)
VTP-500 MERS1
172 — 172
VTP-600 NSCLC2
164 275 (111)
VTP-850 Prostate cancer 178 215 (37)
VTP-1000 Celiac 1,374 1,572 (198)
Other and earlier stage programs3
784 280 504
Total direct research and development expenses $ 5,838 $ 5,798 $ 40
Indirect research and development expenses:
Personnel-related (including share-based compensation) 4,335 3,601 734
Facility related 390 371 19
Other indirect costs 562 44 518
Total indirect research and development expenses 5,287 4,016 1,271
Total research and development expense $ 11,125 $ 9,814 $ 1,311

1The development of VTP-500 is funded pursuant to an agreement with the Coalition for Epidemic Preparedness Innovations (CEPI).
2The VTP-600 NSCLC Phase 1/2a trial is sponsored by Cancer Research UK.
3Research and development expenses related to VTP-1100 HPV Cancer were previously included with VTP-1000 Celiac but are now included in ‘Other and earlier stage programs’ because we are focusing resources on other clinical programs and deferring the IND application for VTP-1100 in HPV cancer.
•General and administrative expenses: General and administrative expenses were $6.0 million in the first quarter of 2024, compared to $12.1 million in the first quarter of 2023. The decrease of $6.1 million relates primarily to a gain of $1.2 million on foreign exchange for the first quarter of 2024, compared to a loss of $3.5 million for the first quarter of 2023, a decrease in personnel expenses, including share-based payment charges of $0.8 million, primarily due to a reduction in non-cash share-based payment charges, and a decrease in insurance costs of $0.9 million due to a reduction in insurance premiums.
•Net loss: For the first quarter of 2024, the Company generated a net loss attributable to its shareholders of $15.5 million, or $(0.40) per share on both basic and fully diluted bases, compared to a net loss attributable to its shareholders of $18.2 million, or $(0.48) per share on both basic and fully diluted bases in the first quarter of 2023.

On May 12, 2024 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported that the National Medical Products Administration (NMPA) in China has approved the New Drug Application (NDA) for AUGTYRO (repotrectinib) for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small-cell lung cancer (NSCLC) (Press release, Zai Laboratory, MAY 12, 2024, View Source [SID1234643106]). The approval is based on the pivotal TRIDENT-1 study, an open-label, single-arm, Phase 1/2 trial that evaluated repotrectinib in TKI-naïve and TKI-pretreated patients with ROS1-positive NSCLC.

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"We are pleased with NMPA’s approval of AUGTYRO for the treatment of patients with ROS1-positive NSCLC in China. There is a significant unmet need for these patients given the limited durability of benefit due to the emergence of resistance with existing therapies, eventually leading to tumor progression," said Rafael G. Amado, M.D., President, Head of Global Oncology Research and Development at Zai Lab. "We appreciate the NMPA for their thorough assessment of AUGTYRO, recognizing its potential to address the unmet medical need in China."

"Despite existing earlier generation TKIs for ROS1-positive NSCLC, there remains an unmet need for new treatment options that support important clinical goals, such as durable therapeutic response," said Dr. Shun Lu, M.D., Ph.D., Chief of Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University. "The TRIDENT-1 study showed that treatment with repotrectinib results in high response rates with promising durability in patients with ROS1-positive NSCLC, across TKI-naïve and TKI-pretreated settings, including in the presence of intracranial disease. Based on this study, repotrectinib has the potential to become a new standard of care for these patients."

In June 2023, China’s NMPA accepted the NDA for AUGTYRO for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC, with priority review granted in May 2023.

Zai Lab contributed to the pivotal TRIDENT-1 study and dosed the first patient in Greater China in May 2021, and the results were published in the New England Journal of Medicine in January 2024. The topline efficacy and safety data of Chinese subpopulation is consistent with that of global population, demonstrating robust response rates and durable clinical activity in patients with ROS1-positive NSCLC. Treatment with AUGTYRO was generally well tolerated with a manageable safety profile.

About AUGTYRO

AUGTYRO (repotrectinib) is a next-generation tyrosine kinase inhibitor targeting the ROS1 and NTRK oncogenic drivers. Patients with solid tumors, including NSCLC, harboring ROS1 and NTRK gene fusions treated with approved targeted therapies often develop resistance mutations that limit binding of these drugs to their target. Ultimately, this leads to shortened duration of response and tumor progression. AUGTYRO is the first next-generation ROS1 and TRK TKI uniquely designed to improve durability of benefit, including in the brain.

In November 2023, AUGTYRO was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC.

AUGTYRO has been granted three Breakthrough Therapy Designations from the U.S. Food and Drug Administration in: ROS1-positive metastatic NSCLC patients who have not been treated with a ROS1 TKI; ROS1-positive metastatic NSCLC patients who have previously been treated with one ROS1 TKI and who have not received prior platinum-based chemotherapy; and patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with one or two prior TRK TKIs, with or without prior chemotherapy, and have not had satisfactory alternative treatments. Additionally, AUGTYRO was previously granted four Fast-Track designations in patients with: ROS1-positive advanced NSCLC who have not been treated with one ROS1 TKI; ROS1-positive advanced NSCLC who have been previously treated with one prior line of platinum-based chemotherapy and one prior ROS1 TKI; ROS1-positive advanced NSCLC pretreated with one prior ROS1 TKI without prior platinum-based chemotherapy; and advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with at least one prior line of chemotherapy and one or two prior TRK TKIs and have not had satisfactory alternative treatments. AUGTYRO was also granted an Orphan Drug designation in 2017.

AUGTYRO has been granted four Breakthrough Therapy Designations by the CDE of China’s NMPA in ROS1-positive metastatic NSCLC patients who have not been treated with a ROS1 TKI; ROS1-positive metastatic NSCLC patients who have previously been treated with one prior ROS1 TKI and who have not received prior platinum-based chemotherapy or immunotherapy; and ROS1-positive metastatic NSCLC patients who have previously been treated with one prior ROS1 TKI and one platinum-based chemotherapy; and patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with one or two prior TRK TKIs, with or without prior chemotherapy, and have not had satisfactory alternative treatments.

Zai Lab has an exclusive license agreement with Turning Point Therapeutics, Inc. (Turning Point Therapeutics, a Bristol Myers Squibb company) to develop and commercialize AUGTYRO in Greater China (Mainland China, Hong Kong, Taiwan, and Macau).

About TRIDENT-1

TRIDENT-1 is a global, multicenter, single-arm, open-label, multi-cohort Phase 1/2 clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of AUGTYRO in patients with advanced solid tumors, including NSCLC.1,2 Phase 1/2 includes patients with locally advanced or metastatic solid tumors harboring ROS1 fusions.2 Additional analyses of the trial are still being conducted; asymptomatic central nervous system (CNS) metastases are allowed.1,2 The trial excludes patients with symptomatic brain metastases, among other exclusion criteria.1 Phase 1 of the trial included the dose escalation that determined the recommended Phase 2 dose.2

Phase 2 of the trial has a primary endpoint of overall response rate (ORR).1,2 Key secondary endpoints include duration of response (DOR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by Blinded Independent Central Review (BICR), progression-free survival (PFS), and intracranial response in six distinct expansion cohorts, including TKI-naïve and TKI-pretreated patients with ROS1-positive locally advanced or metastatic NSCLC.1,2

In TRIDENT-1, 79% (95% Confidence Interval [CI]: 68 to 88) of TKI-naïve patients (n=71) responded to treatment; 6% experienced complete responses and 73% experienced partial responses.1 The median duration of response (mDOR) was 34.1 months.1 Among TKI-pretreated patients, 38% (95% CI: 25 to 52) (n=56) responded to treatment; 5% experienced complete responses and 32% experienced partial responses and the mDOR was 14.8 months.1 Among those who had measurable CNS metastases at baseline, responses in intracranial lesions were observed in 7 of 8 TKI-naïve patients and in 5 of 12 of those who were TKI-pretreated.1

The FDA-approved dosing for AUGTYRO is 160 mg orally once daily for 14 days, then increased to 160 mg twice daily until disease progression or unacceptable toxicity.1

About Non-Small Cell Lung Cancer in China

Lung cancer is the most commonly diagnosed cancer type and the leading cause of cancer death in China. There were approximately 871,000 new cases and 767,000 deaths of lung cancer in China in 2022, respectively.3 NSCLC accounts for approximately 85% of lung cancer, and approximately 70% of NSCLC is locally advanced or metastatic at initial diagnosis. In China, ROS1 rearrangements occur in 2-3% of patients with advanced NSCLC.