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.

On May 12, 2024 Photocure ASA (OSE: PHO), the Bladder Cancer Company, announces that its partner Asieris Pharmaceuticals (SSE: 688176) communicated today that the National Medical Products Administration (NMPA) has accepted its new drug application (NDA) for the regulatory review of Cevira (APL-1702, Hexaminolevulinate Hydrochloride Ointment Photodynamic Therapy System) for potential marketing authorization in China. Cevira (APL-1702) is a photodynamic drug-device combination product in development for the non-surgical treatment of high-grade squamous intraepithelial lesions (HSIL), licensed to Asieris by Photocure.

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"We are pleased that Cevira continues to advance toward market approval in China, as it can serve an important non-invasive option to treat pre-cervical cancer without the complications of surgical intervention," said Dan Schneider," President and CEO of Photocure. "Asieris continues to be a valued partner to Photocure, with solid execution on both programs that it has licensed from us. We look forward to further announcements on the regulatory progress of Cevira as well as Asieris’ pending NDA for Hexvix in China."

The Asieris media release states: "APL-1702 is a first-in-class, non-surgical treatment for cervical HSIL with its efficacy proven in an international phase III trial. It heralds a potential paradigm shift in the treatment of precancerous cervical lesions, with the clinical focus moving from excision to long-term disease management. Emphasis lies in optimizing the delicate balance between treatment risks and benefits, striving to minimize or delay invasive procedures while effectively reversing the progression of the disease.

On May 12, 2024 SCG Cell Therapy Pte Ltd (SCG), a clinical-stage biotechnology company developing novel immunotherapies for infectious diseases and their associated cancers, reported first preclinical data of its novel human papillomavirus (HPV)-specific T cell receptor-engineered T (TCR T) cell therapy armored with an TGFβRII-41BB immunoswitch – SCG142 – in an oral presentation at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting in Baltimore, Maryland (Press release, SCG Cell Therapy, MAY 12, 2024, View Source [SID1234643104]).

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In preclinical studies, SCG142 demonstrated superior CD8+ and CD4+ TCR T cell proliferation and tumor inhibition both in-vitro and in-vivo compared to conventional TCR T without immunoswitch, including tumor rechallenge models. Importantly, SCG142 functionality is CD8 co-receptor independent, transferring desired effector functions also to CD4+ T cells and promoting longer persistence and improved proliferation of T cells. In addition, SCG142 exhibited high functional avidity and can recognize both genotypes HPV-16 and HPV-52, with a favorable safety profile with no alloreactivity or off-target toxicity in relevant toxicology models.

"SCG142 is a novel and differentiated HPV-specific TCR T cell therapy with preclinical efficacy in various tumor types with expression of HPV-16- and HPV-52 genotypes. We’re excited to demonstrate that armoring the TCR-T cells with the chimeric switch receptor didn´t change the favorable safety profile but helped to overcome the immune inhibitory signal of TGF-β, which can be crucial for effective treatment of solid tumors", said Dr. Susanne Wilde, Head of Preclinical Research of SCG Cell Therapy. "These promising results underscore the potential of SCG142 to provide new solutions for patients in a variety of HPV-16- and HPV-52 expressing cancers. Based on these encouraging data, we are eagerly advancing SCG142 towards clinical trials", she added.

About SCG142
SCG142, an autologous HPV-specific TCR T cell therapy holding the promise as the best-in-class product. Utilizing SCG’s proprietary GianTCRTM technology, high affinity and high avidity natural TCRs can be isolated to target against intracellular antigens presented through major histocompatibility complex (MHC) in solid tumors. Study results showed that SCG142, a fully natural HPV specific TCR armoured with chimeric switch receptor, has the potential to specially target HPV-16 and HPV-52-positive tumor cells in various HPV-related tumor types, generating CD8 co-receptor independent T cell functionality and sustained anti-tur activity.

About Human Papillomavirus and Cancers
Human papillomavirus (HPV) infection is the most common sexually transmitted infection. Nearly all sexually active people are infected with HPV and around half of these infections occur with a high-risk HPV type, which can lead to cancer development.1 As such, HPV infection accounts for more than 90% of anal and cervical cancers, about 70% of vaginal and vulvar cancers, and 60% of penile and oropharyngeal cancers, and it causes an estimated 630,000 cancers worldwide each year.

On May 11, 2024 Replicate Bioscience, a clinical-stage company pioneering novel self-replicating RNA (srRNA) technology for use across a range of infectious disease, oncology, autoimmune disease indications and beyond, reported new preclinical data and today will share interim clinical trial results from an ongoing Phase 1 study at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting, May 7-11 in Baltimore, Maryland (Press release, Replicate Bioscience, MAY 11, 2024, View Source;cell-therapy-asgct-annual-meeting-302142558.html [SID1234643103]).

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"At ASGCT (Free ASGCT Whitepaper), Replicate is presenting two important breakthroughs in srRNA technology," said Nathaniel Wang, Ph.D., CEO of Replicate. "For vaccines, our clinical data demonstrate the induction of protective levels of immunity at doses significantly lower than any other reported mRNA or srRNA vaccine. This potency, combined with a best-in-class safety profile, demonstrates the capability of our technology to greatly expand the utility of RNA technology for vaccines. Beyond vaccines, further improvements to our library of vectors now enable us to control and prolong in vivo production of therapeutic proteins compared to circular RNA, linear mRNA, and current state-of-the art srRNA, opening up therapeutic areas such as immunology and metabolic disease."

RBI-4000’s Phase 1 results will be presented on Saturday, May 11 at 10:15 a.m. ET by Replicate’s Chief Medical Officer, Zelanna Goldberg, M.D., in an oral presentation titled "Single and Low Dose Self-Replicating RNA Vaccine Provides Effective Immune Protection Against Rabies in Healthy Volunteers." The results highlight the strong immunogenicity and favorable safety profile of RBI-4000 in the Phase 1 trial, which is the first clinical validation of Replicate’s next-generation srRNA technology. Additional takeaways are as follows:

Day 85 datasets for all cohorts met the WHO-established surrogate of protection at doses significantly lower than any other reported RNA-based vaccines;
Substantive majority of participants achieved metric in all dose cohorts.
In the previously unreported 10 mcg dose cohorts:
100% of participants achieved surrogate of protection after two vaccine doses.
92% of participants achieved surrogate of protection after a single vaccine dose.
Safety data from the interim dataset demonstrate RBI-4000 was well tolerated with no severe adverse events across all cohorts; reactogenicity was transient and self-limiting.
No dose limiting toxicity (DLT) was observed; maximum tolerated dose (MTD) has not been reached, enabling further dose escalation.
On May 9, Parinaz (Paris) Aliahmad, Ph.D., Head of Research and Development at Replicate, delivered an oral presentation at ASGCT (Free ASGCT Whitepaper) titled "Novel Self-Replicating RNA Vectors Broaden Therapeutic Window and Expand Use Outside of Vaccines." The results underscore the broad potential of srRNA as a new treatment modality across a wide range of disease areas. Additional takeaways are as follows:

Vaccines using Replicate’s optimized vectors achieve protective immunity at ultra-low doses (1 picogram) with minimal reactogenicity.
Beyond vaccines, Replicate’s novel srRNA vectors demonstrate >100-fold increased expression of encoded proteins and improved durability compared to circular RNA, linear mRNA vectors, and current state-of-the-art srRNA technologies.
Replicate’s novel srRNA vectors can expand utility of RNA technology for templated expression of biotherapeutic proteins for applications outside of vaccines, in areas such as immune disorders, metabolic disease, and cancers.

On May 10, 2024 Cytimm, a clinical-stage company focused on the development of IL-2 based therapeutics for cancer, autoimmune diseases, and neurodegenerative diseases, reported that Dr. Haining Huang, Co-Founder and Chief Executive Officer, would present a corporate overview next month at the 2024 BIO International Convention in San Diego (Press release, Cytimm Therapeutics, MAY 10, 2024, View Source [SID1234646047]). The presentation is set for 11:00 a.m. PDT on Wednesday, June 5, 2024 in Company Presentation Theater 1 in Hall A of the Exhibition Hall at the San Diego Convention Center.

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Dr. Huang will provide an overview of Cytimm’s strategies and innovative technologies in decoupling the two opposite functions of IL-2 and the development of the two proprietary IL-2 based drugs, CTM103 and CTM201.

CTM103 is a mRNA drug that encodes HSA-IL2v fusion protein, for the treatment of solid tumors. This intravenously delivered drug can efficiently and continuously expresses IL2v with a significantly prolonged half-life. Clinical trials of CTM103 as monotherapy or in combination with Pembrolizumab demonstrated good safety andPK profiles as well as robust immune stimulatory activity in promoting CD8 T cells and NK cells proliferation. Encouraging signs of antitumor efficacy warrants more dose escalations and cohort expansions in selected tumor indication like NSCLC, HNSCC, RCC, melanoma and others.

CTM201 is the first Treg specific long-acting PEG-IL2 without compromising its bioactivity. Cytimm, for the first time, identified the ideal PEGylation strategy for IL-2 with improved activity, stability and functionality. Based on our proprietary PEGylation technology platform, CTM201 was developed as the immune suppressor for inflammatory diseases including autoimmune diseases and neurodegenerative diseases. FIH studies in ALS volunteers demonstrated excellent safety profile and robust Treg specific amplification.

In the presentation, we will highlight our recent progress in developing next-generation IL-2 based therapies in cancer and chronic inflammatory indications. This is an exciting time for Cytimm, and we look forward to sharing our views and progresses with the community at the BIO conference in San Diego. BIO is the industry’s largest and most prestigious event and we appreciate the selection of Cytimm as a presenting company that will be featured in the partnering section of the conference.

Cytimm will also hold One-on-One meets with potential partners in the event. To schedule a meeting at the BIO International Convention with Cytimm, please submit a meeting request through the BIO One-on-One Partnering platform. For more information, please visit BIO websites or send an e-mail to Cytimm at [email protected].