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 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 Instil Bio, Inc. ("Instil") (Nasdaq: TIL), a clinical-stage biopharmaceutical company focused on developing a pipeline of novel therapies, reported its first quarter 2024 financial results and provided a corporate update (Press release, Instil Bio, MAY 10, 2024, View Source [SID1234643083]).

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Recent Highlights:

With successful completion of feasibility studies, preparations are underway with collaborator for a potential investigator-initiated trial (IIT) in non-small cell lung cancer with folate receptor α (FRα)-CoStAR TIL
Exploring opportunities to in-license/acquire and develop novel therapeutic candidates in diseases with significant unmet medical need
Cash runway expected beyond 2026
First Quarter 2024 Financial and Operating Results:

As of March 31, 2024, Instil had cash, cash equivalents, marketable securities and long-term investments of $161.5 million, which consisted of $5.5 million in cash and cash equivalents, $148.3 million in marketable securities and $7.7 million in long-term investments, compared to $175.0 million in total cash, cash equivalents, restricted cash, marketable securities and long-term investments, which consisted of $9.2 million in cash and cash equivalents, $1.5 million in restricted cash, $141.2 million marketable securities and $23.2 million in long-term investments as of December 31, 2023. Instil expects that its cash, cash equivalents, marketable securities and long-term investments as of March 31, 2024 will enable it to fund its current operating plan beyond 2026.

Research and development expenses were $7.3 million for the three months ended March 31, 2024, compared to $20.7 million for the three months ended March 31, 2023.

General and administrative expenses were $12.4 million for the three months ended March 31, 2024, compared to $13.2 million for the three months ended March 31, 2023.

Restructuring and impairment charges were $4.3 million for the three months ended March 31, 2024, compared to $24.6 million for the three months ended March 31, 2023.

Net loss per share, basic and diluted were $3.74 for the three months ended March 31, 2024, compared to $8.77 for the three months ended March 31, 2023. Non-GAAP net loss per share, basic and diluted were $2.39 for the three months ended March 31, 2024, compared to $4.29 for the three months ended March 31, 2023.

Note Regarding Use of Non-GAAP Financial Measures

In this press release, Instil has presented certain financial information that has not been prepared in accordance with U.S. generally accepted accounting principles ("GAAP"). These non-GAAP financial measures include non-GAAP net loss and non-GAAP net loss per share, which are defined as net loss and net loss per share, respectively, excluding non-cash stock-based compensation expense and restructuring and impairment charges. Instil believes that these non-GAAP financial measures, when considered together with the GAAP figures, can enhance an overall understanding of Instil’s financial performance. The non-GAAP financial measures are included with the intent of providing investors with a more complete understanding of Instil’s operating results. In addition, these non-GAAP financial measures are among the indicators Instil’s management uses for planning purposes and to measure Instil’s performance. These non-GAAP financial measures should be considered in addition to, and not as a substitute for, or superior to, financial measures calculated in accordance with GAAP. The non-GAAP financial measures used by Instil may be calculated differently from, and therefore may not be comparable to, non-GAAP financial measures used by other companies. Please refer to the below reconciliation of these non-GAAP financial measures to the comparable GAAP financial measures.

On May 10, 2024 Novartis reported that the FDA has granted Breakthrough Therapy designation to Scemblix (asciminib) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) (Press release, Novartis, MAY 10, 2024, View Source [SID1234643084]). This marks the third1 Breakthrough Therapy designation for Scemblix.

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According to FDA guidelines, treatments that receive Breakthrough Therapy designation must target a serious or life-threatening disease and demonstrate a potential substantial improvement over existing therapies on one or more clinically significant endpoints.
Breakthrough Therapy designation was granted based on positive data from the Phase III ASC4FIRST study, in which Scemblix met both primary endpoints with superior MMR rates at week 48 compared to investigator-selected TKIs (imatinib, nilotinib, dasatinib and bosutinib) and compared to imatinib alone. Scemblix also demonstrated a favorable safety and tolerability profile with fewer adverse events (AEs) and treatment discontinuations vs. standard-of-care TKIs.
With current standard-of-care TKIs, approximately half2 of newly diagnosed patients with CML fail to meet molecular response goals at one year, and many discontinue or change treatment due to intolerance.
Full results of the ASC4FIRST study will be presented at ASCO (Free ASCO Whitepaper) on Friday, May 31. Novartis is also hosting an in-person investor event in Chicago on Sunday, June 2, to delve deeper into the results and the potential commercial opportunity for Scemblix in 1L CML upon regulatory approval.

Overall, Novartis has received 30 approvals for Breakthrough Therapy designated drugs, reflecting our track record of innovation.

On May 10, 2024 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported its recent accomplishments and financial results for the quarter ended March 31, 2024 (Press release, Soligenix, MAY 10, 2024, View Source [SID1234643085]).

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"Recently we completed a public offering with gross proceeds of approximately $4.75 million, which will allow us to continue to move our rare disease pipeline forward," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "While we continue our ongoing discussions with the United States (U.S.) Food and Drug Administration (FDA), we shared that the European Medicines Agency (EMA) has agreed to the study design of a confirmatory Phase 3 placebo-controlled study evaluating the safety and efficacy of HyBryte (synthetic hypericin) in the treatment of cutaneous T-cell lymphoma (CTCL) patients with early-stage disease. This study will enroll approximately 80 patients across the U.S. and Europe, starting before the end of 2024, with top-line results expected in the second half of 2026. We also will be initiating a Phase 2 study with SGX945 (dusquetide) in Behçet’s disease later this year with top-line results expected in the first half of 2025, along with top-line results expected during the same timeframe from our ongoing SGX302 (synthetic hypericin) Phase 2 study in mild-to-moderate psoriasis. Additionally, we were recently granted orphan drug designations from the FDA’s Office of Orphan Products Development for the active ingredients in both SuVax, for "the prevention and post-exposure prophylaxis against Sudan ebolavirus (SUDV) infection and MarVax, for "the prevention and post-exposure prophylaxis against Marburg marburgvirus (MARV) infection."

Dr. Schaber continued, "With approximately $7.1 million in cash at March 31, 2024, exclusive of the approximate $4.3 million in net proceeds from our recent financing and our non-dilutive government funding, we continue to manage cash burn very carefully to achieve our near-term milestones. We have a clear vision for the future, and we are actively pursuing new opportunities to create long-term value for our shareholders including but not limited to, partnership and merger and acquisition opportunities."

Soligenix Recent Accomplishments

On April 25, 2024, the Company announced it had received notice of intent to grant additional patents based on its patent application titled "Compositions and Methods of Manufacturing Trivalent Filovirus Vaccines" in the United Kingdom and South Africa, with other international jurisdictions pending. To view this press release, please click here.
On April 18, 2024, the Company announced the pricing of its public offering of 11,875,000 shares of common stock (or common stock equivalents in lieu thereof) and warrants to purchase up to 11,875,000 shares of common stock at a combined public offering price of $0.40 per share and accompanying warrants for aggregate gross proceeds of approximately $4.75 million, before deducting placement agent fees and other offering expenses. To view this press release, please click here.
On April 15, 2024, the Company announced the Office of Orphan Products Development of the U.S. FDA had granted orphan drug designation to the active ingredient in SuVax, the subunit protein vaccine of recombinantly expressed SUDV glycoprotein, for "the prevention and post-exposure prophylaxis against SUDV infection." To view this press release, please click here.
On April 11, 2024, the Company announced the Office of Orphan Products Development of the U.S. FDA had granted orphan drug designation to the active ingredient in MarVax, the subunit protein vaccine of recombinantly expressed MARV glycoprotein, for "the prevention and post-exposure prophylaxis against MARV infection." To view this press release, please click here.
On April 3, 2024, the Company announced it had received agreement from the EMA on the key design components of a confirmatory Phase 3 placebo-controlled study evaluating the safety and efficacy of HyBryte (synthetic hypericin) in the treatment of CTCL patients with early-stage disease. To view this press release, please click here.
Financial Results – Quarter Ended March 31, 2024

Soligenix’s revenues for the quarter ended March 31, 2024 were $0.1 million as compared to $0.3 million for the quarter ended March 31, 2023. Revenues primarily relate to government contracts and grants awarded in support of SGX943 for treatment of emerging and/or antibiotic-resistant infectious diseases; development of CiVax, our vaccine candidate for the prevention of COVID-19, and evaluation of HyBryte for expanded treatment in patients with early-stage CTCL.

Soligenix’s net loss was $1.9 million, or ($0.18) per share, for the quarter ended March 31, 2024, as compared to $1.0 million, or ($0.36) per share, for the quarter ended March 31, 2023. The increase in net loss was primarily due to the recognition of an income tax benefit during the three months ended March 31, 2023 with no corresponding income tax benefit recognized during the three months ended March 31, 2024.

Research and development expenses were $1.1 million as compared to $0.9 million for the quarters ended March 31, 2024 and 2023, respectively. The increase was primarily due to an increase in preliminary costs associated with the anticipated initiation of our Phase 2 study in Behçet’s Disease and the second confirmatory Phase 3 CTCL trial.

General and administrative expenses were $1.0 million and $1.2 million for the quarters ended March 31, 2024 and 2023, respectively. This decrease in general and administrative expenses is primarily attributable to a reduction in legal and professional fees associated with the reverse stock split of our issued and outstanding shares of common stock during the three months ended March 31, 2023.

As of March 31, 2024, the Company’s cash position, exclusive of the approximate $4.3 million in net proceeds from our recent financing, was approximately $7.1 million.