On October 28, 2022 ASLAN Pharmaceuticals (Nasdaq: ASLN), a clinical-stage, immunology-focused biopharmaceutical company developing innovative treatments to transform the lives of patients, reported financial results for the third quarter ended September 30, 2022, and provided an update on recent corporate activities (Press release, ASLAN Pharmaceuticals, OCT 28, 2022, View Source [SID1234622575]).

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"In the third quarter we presented a number of new and important insights on eblasakimab’s differentiated mechanism of action in neuronal itch and inflammatory pathways, and the potential improvements for AD patients related to itch and sleep loss, which are often the most burdensome symptoms reported by these patients," shared Dr Carl Firth, CEO, ASLAN Pharmaceuticals. "We look forward to the topline readout of Phase 2b data evaluating eblasakimab in biologic naïve moderate-to-severe AD patients in Q2 2023. In the lead up to the new data that we will generate from both TREK-AD and TREK-DX, we are building a robust set of insights from ongoing research collaborations that will be presented early next year, to support eblasakimab’s potential as a differentiated treatment for moderate-to-severe AD with broad therapeutic potential in Type 2-driven inflammatory diseases."

Third quarter 2022 and recent business highlights

Eblasakimab

In August, the Company signed a licensing agreement with Belle.ai for the use of belleStudy digital image capture software across several global sites in the ongoing TREK-AD study of eblasakimab in AD. The easy-to-use solution enables standardized recording of AD disease severity scores through image capture and the technology will allow ASLAN to further enhance its quality control procedures in the TREK-AD study.
In September, three posters with new data on biomarkers, efficacy measures and patient reported outcome measures from the previously reported Phase 1b proof-of-concept trial of eblasakimab were presented at the 31st European Academy of Dermatology and Venereology (EADV) annual congress. The data showed eblasakimab suppresses downstream inflammatory biomarkers of AD, and this effect continues four to six weeks after the last dose administered. Patients treated with eblasakimab demonstrated notable improvements in quality-of-sleep measures and eblasakimab was shown to reduce P-NRS (itch) scores versus placebo, with improvements throughout the eight-week course of treatment across all dose cohorts. The posters can be found in the News and Publications section of the Company’s website.
In September, the Company commenced TREK-DX (TRials in EblasaKimab in Dupilumab eXperienced AD patients), a new clinical trial studying eblasakimab in dupilumab-experienced moderate-to-severe AD patients. The trial consists of a 16-week treatment period and a 12-week safety follow-up period. The primary efficacy endpoint is percentage change in Eczema Area Severity Index (EASI) score from baseline to week 16. In combination with the data from biologic naïve AD patients in the TREK-AD trial, we believe the results from the TREK-DX study in the biologic-experienced population could position eblasakimab as a preferred first choice treatment for moderate-to-severe AD.
The Company hosted a Research and Development Day in September where management gave a comprehensive update on the eblasakimab development program. Dr Peter A Lio, from Northwestern University Feinberg School of Medicine, and Dr Shawn Kwatra, from Johns Hopkins University, discussed the emerging unmet needs, therapeutic landscape and underlying molecular mechanisms in AD and Type 2-driven diseases. A replay of the event and presentation materials can be found in the Investor Relations section of the Company’s website.
In September, the Company presented new translational data on eblasakimab at the late-breaker session of the European Society for Dermatological Research (ESDR) annual meeting. The first data from the ongoing collaboration with Dr Shawn Kwatra and Dr Madan Kwatra showed increased IL-13Rα1 expression on mast cells and eosinophils in skin samples from AD patients, reinforcing the central role of IL-13Rα1 in AD. In human neuron models, eblasakimab significantly reduced neuronal itch sensitization caused by distinct IL-4 and IL-13 itch pathways and an emerging role of IL-13Rα1 signaling in mediating neuronal excitability and sensitivity beyond AD was also identified.
Farudodstat (ASLAN003)

A clinical development plan in skin autoimmune diseases is being finalized and a Phase 2 trial is expected to commence in the first half of 2023.
Anticipated upcoming milestones

First patient enrolled in the TREK-DX trial by the end of 2022.
New translational data highlighting the unique effects of eblasakimab’s mechanism of action will be presented in early 2023.
Topline data from the Phase 2b TREK-AD trial of eblasakimab is expected in Q2 2023.
Third quarter 2022 financial highlights

Cash used in operating activities for the third quarter of 2022 was US$9.1 million compared to US$7.6 million in the same period in 2021.
Cash, cash equivalents and short-term investments as of September 30, 2022, were US$68.9 million.
Research and development expenses were US$8.0 million in the third quarter of 2022 compared to US$5.3 million in the third quarter of 2021. The increase was due to clinical development and manufacturing costs for eblasakimab.
General and administrative expenses were US$2.3 million in the third quarter of 2022 compared to US$2.8 million in the third quarter of 2021.
Net loss attributable to stockholders for the third quarter of 2022 was US$10.9 million compared to a net loss of US$8.6 million for the third quarter of 2021.
The weighted average number of American Depositary Shares (ADS) outstanding in the computation of basic loss per share for the third quarter of 2022 was 69.7 million (representing 348.7 million ordinary shares), the same as the third quarter of 2021. One ADS is the equivalent of five ordinary shares.

On October 28, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported the initial data from the Phase 1 dose-escalation portion of its ongoing ARROS-1 Phase 1/2 clinical trial of NVL-520 for patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) and other solid tumors (Press release, Nuvalent, OCT 28, 2022, View Source [SID1234622574]). These data will be presented today in the "New Drugs on the Horizon" oral plenary session at the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium in Barcelona, Spain.

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NVL-520 is a novel brain-penetrant ROS1-selective inhibitor created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, off-target central nervous system (CNS) adverse events, and brain metastases that may limit the use of currently available ROS1 tyrosine kinase inhibitors (TKIs).

"Currently approved and investigational ROS1 TKIs are important treatment options for advanced ROS1 fusion-positive cancers. However, these drugs can have key limitations. These include the inability to treat on-target resistance and brain metastases effectively, and an association with neurologic adverse events," said Alexander Drilon, M.D., Chief, Early Drug Development Service, Memorial Sloan Kettering Cancer Center (MSK) and presenting investigator. "These preliminary data support NVL-520 as a potential best-in-class ROS1-selective inhibitor that may combine, for the first time, potent and selective targeting of diverse ROS1 fusions and secondary ROS1 resistance mutations including G2032R, brain penetrance, and the avoidance of TRK inhibition that can be dose limiting."

As of September 1, 2022, 35 subjects have been enrolled in the Phase 1 portion of the ARROS-1 trial. Treatment with NVL-520 across five evaluated dose levels ranging from 25 mg once daily (QD) to 125 mg QD resulted in exposures above all target efficacy thresholds. As of the preliminary data cut-off date of September 13, 2022, no dose-limiting toxicities (DLTs), treatment-related serious adverse events (SAEs), treatment-emergent dizziness, or adverse events leading to treatment reductions or discontinuations were observed.

Preliminary activity data reported as of the data cut-off date were available from 21 heavily pre-treated response-evaluable NSCLC patients, of which partial responses were observed in 48% (10/21). To evaluate key target characteristics of NVL-520, activity was examined in subgroups including:

Patients with ROS1 G2032R mutations (Objective Response Rate (ORR) 78%, 7/9);

Patients with a history of CNS metastases (ORR 73%, 8/11);

The most heavily pre-treated of patients, receiving two or more prior ROS1 TKIs and one or more prior lines of chemotherapy (ORR 53%, 9/17); and

Patients previously treated with lorlatinib or repotrectinib (ORR 50%, 9/18).

As of the preliminary data cut-off date, 76% (16/21) of response-evaluable patients continued on NVL-520 treatment. Enrollment in the Phase 1 portion of the trial is ongoing.

"We are excited to present the first look at the safety and clinical activity of NVL-520 from our ARROS-1 clinical trial, which we believe supports NVL-520 as a potential best-in-class ROS1-selective inhibitor that may be capable of overcoming the limitations of current approved and investigational ROS1 TKIs," said Christopher Turner, M.D., Chief Medical Officer of Nuvalent. "Across all evaluated dose levels, NVL-520 exhibited activity in a heavily pre-treated patient population, many of whom have exhausted all available treatment options and would have been excluded from other investigational ROS1 TKI studies. Importantly, the favorable safety profile and lack of dose reductions or discontinuations due to adverse events reflected in this preliminary data suggest that NVL-520 has the potential to provide deep and durable responses and may be able to move up in the treatment paradigm for patients with ROS1-driven cancers."

"We believe today’s preliminary results further support Nuvalent’s approach of applying innovative chemistry and structure-based drug design to well-defined target product profiles focused on addressing medical needs that have been identified in collaboration with leading physician-scientists," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "Not only has this approach rapidly delivered the encouraging preliminary results for NVL-520 presented today, it underpins our work

across our entire pipeline, including parallel lead candidate NVL-655 for ALK-positive NSCLC, and our recently announced development candidate for HER2ex20-driven cancers, NVL-330. I congratulate the entire Nuvalent team for their dedication and tireless efforts, and offer sincere gratitude to the patients, caregivers and investigators who are participating in the ARROS-1 trial."

NVL-520 First-In-Human Preliminary Phase 1 Data

NVL-520 is currently being evaluated in the ongoing ARROS-1 Phase 1/2 clinical trial, a first-in-human study of NVL-520 in patients with advanced ROS1-positive NSCLC and other solid tumors. The Phase 1 dose escalation portion is enrolling ROS1-positive NSCLC patients who have previously received at least one ROS1 TKI, or patients with other ROS1-positive solid tumors who have been previously treated. The Phase 1 portion of the trial is designed to evaluate the overall safety and tolerability of NVL-520, with additional objectives including determination of the recommended Phase 2 dose (RP2D), characterization of the pharmacokinetic profile, and evaluation of preliminary anti-tumor activity.

As of September 1, 2022, 35 subjects were enrolled in the Phase 1 portion of the ARROS-1 trial, of which 34 patients had ROS1-positive NSCLC and 51% (18/35) had a history of CNS metastases.

The patient population was heavily pre-treated:

77% (27/35) had received three or more prior lines of anti-cancer therapy;

71% (25/35) had received two or more prior ROS1 TKIs and one or more lines of chemotherapy; and

80% (28/35) had received a ROS1 TKI other than crizotinib or entrectinib, including lorlatinib (57%, 20/35) or repotrectinib (34%, 12/35).

Preliminary Safety and Pharmacokinetic Analysis

Preliminary safety and pharmacokinetics of NVL-520 were evaluated as of the data cut-off date of September 13, 2022. Patients were treated in five dose cohorts of 25 mg, 50 mg, 75 mg, 100 mg, or 125 mg once daily NVL-520.

NVL-520 demonstrated exposure above all target efficacy thresholds (ROS1 wild type and ROS1 G2032R in both the periphery and in the CNS). Favorable pharmacokinetics and low intra-cohort patient PK variability were observed, with exposure increasing with increasing dose level and half-life supportive of once daily dosing.

A favorable preliminary safety profile was observed with NVL-520 treatment in the 35 patients enrolled across the dose-escalation portion of ARROS-1, suggesting the potential for a highly ROS1-selective, TRK sparing design. There were no DLTs, no treatment-related SAEs, no treatment related dizziness, and no adverse events leading to dose reduction or discontinuation of NVL-520 through the preliminary data cut-off date.

Most treatment-related adverse events (TRAEs) were low-grade and manageable, and the favorable preliminary safety profile allowed for achievement of exposure levels well above target thresholds for both ROS1 and ROS1 resistance variants in both the CNS and the periphery. To date, a maximum tolerated dose has not been reached and Phase 1 is ongoing

to determine the RP2D.

Preliminary Activity Analysis

As of the preliminary data cut-off date of September 13, 2022, 21 patients with NSCLC were response-evaluable by investigator assessment with duration of treatment ranging from one to more than eight months.

Key findings include early anti-tumor activity in ROS1-positive NSCLC patients, including objective responses (RECIST 1.1) in:

Heavily pre-treated patients: Partial Responses (PRs) were observed in 48% (10/21) of all response-evaluable patients, with 76% (16/21) continuing on treatment. Responses were observed in 53% (9/17) of patients who received two or more prior TKIs and one or more prior lines of chemotherapy, in 50% (9/18) of patients previously treated with lorlatinib or repotrectinib, and across all dose levels evaluated.

Patients with ROS1 G2032R resistance mutation: Of nine patients with known ROS1 G2032R resistance mutation, responses were observed in 78% (7/9) including in two of three patients previously treated with repotrectinib, and tumor shrinkage was observed in 100% (9/9). Notably, complete clearance of G2032R allele was observed in all seven patients with G2032R detected on central ctDNA analysis.

Patients with CNS metastases: Intracranial PRs were observed in 100% (3/3) patients with measurable (>10 mm) CNS metastases. Responses were observed in 73% (8/11) of patients with a history of CNS metastases, and no CNS progression was observed in any of the 35 treated patients.

Combined with the favorable tolerability observed across the dose levels evaluated through the preliminary data cut-off date, these data also suggest that NVL-520 is a potential best-in-class therapy that may be able to move up the treatment paradigm for patients with ROS1-positive NSCLC.

The ARROS-1 clinical trial is continuing to enroll patients in the Phase 1 portion of the trial and is focused on further characterizing the safety profile of NVL-520, its pharmacokinetic profile, and determining the RP2D.

Once a safe and tolerable dose is determined as the RP2D, the trial is designed to transition directly into the Phase 2 portion, which will evaluate the overall activity of NVL-520 in several expansion cohorts of patients defined based on the number and type of prior anti-cancer therapies they have received. The Phase 2 cohorts are designed to support potential registration in patients with ROS1-positive NSCLC who are kinase inhibitor-naïve and in those who have been previously treated with ROS1 kinase inhibitors.

Webcast and Conference Call Information

Nuvalent will host a live webcast and conference call today at 8:30am EDT to discuss these results. The event is accessible through the "Events" section of the Investors page of www.nuvalent.com or by dialing (866) 652-5200 (domestic) or (412) 317-6060 (international) and referring to conference ID 10171503. A replay and accompanying slides will be archived on the Nuvalent website for 30 days.

About NVL-520

NVL-520 is a novel brain-penetrant ROS1-selective inhibitor designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with the prevalent G2032R resistance mutation and those with the S1986Y/F, L2026M, or D2033N resistance mutations. NVL-520 has been designed for brain penetrance to potentially improve treatment options for patients with brain metastases. NVL-520 has been observed in preclinical studies to selectively inhibit wild-type ROS1 and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and drive more durable responses for patients. NVL-520 is currently being investigated in the ARROS-1 trial (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors.

On October 28, 2022 Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) (Aurinia or the Company) reported that it will release financial and operational results for third quarter 2022 on Thursday, November 3, 2022, before markets open (Press release, Aurinia Pharmaceuticals, OCT 28, 2022, View Source [SID1234622573]). Aurinia’s management team will host a conference call/webcast at 8:30 am ET that day to review these results and provide a general business update.

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Interested participants can dial 877-407-9170 (Toll-free U.S. & Canada). The audio webcast can also be accessed under "News/Events" through the "Investors" section of the Aurinia corporate website at www.auriniapharma.com. A replay of the webcast will be available on Aurinia’s website.

On October 28, 2022 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported the outcome of the meeting of the U.S. Food and Drug Administration ("FDA") Oncologic Drugs Advisory Committee ("ODAC"), which reviewed investigational 131I-omburtamab ("omburtamab") for the treatment of CNS/leptomeningeal metastasis from neuroblastoma (Press release, Y-mAbs Therapeutics, OCT 28, 2022, View Source [SID1234622572]). The committee voted 16 to 0 that the Company had not provided sufficient evidence to conclude that omburtamab improves overall survival.

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"We are disappointed by the outcome of today’s meeting, as patients with CNS/leptomeningeal metastasis from neuroblastoma are in need of effective and safe treatment options," said Thomas Gad, President, and Interim Chief Executive Officer. "Y-mAbs is committed to working closely with the FDA on their review of the Biologic License Application ("BLA") for omburtamab ahead of their decision. We want to thank all of the patients, caregivers, and healthcare providers who participated in the studies of this life-threatening condition."

ODAC reviewed data from omburtamab’s clinical development program with a focus on study 03-133 (a pivotal phase 1 study) and study 101 (a pivotal phase 2 study) as well as the historical control group.

Y-mAbs BLA submission for omburtamab was accepted for Priority Review by the FDA on May 31, 2022, with a Prescription Drug User Fee Act ("PDUFA") target date of November 30, 2022. The FDA is not bound by the Advisory Committee’s recommendations but generally takes the recommendation into consideration when making its decision.

Researchers at MSK developed omburtamab, which is exclusively licensed by MSK to Y-mAbs. As a result of this licensing arrangement, MSK has institutional financial interests in the compound.

On October 28, 2022 ARCA biopharma, Inc. (Nasdaq: ABIO), a biopharmaceutical company applying a precision medicine approach to developing genetically targeted therapies for cardiovascular diseases, reported third quarter 2022 financial results and provided a corporate update (Press release, Arca biopharma, OCT 28, 2022, View Source [SID1234622571]).

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In May 2022, the Company retained Ladenburg Thalmann & Co. Inc. to act as its financial advisor to explore and evaluate strategic options for maximizing stockholder value. Potential strategic alternatives that may be explored or evaluated as part of this process include the potential for an acquisition, merger, business combination or other strategic transaction involving the Company. The Board has not set a timetable for the conclusion of this review, nor has it made any decisions related to any further actions or potential strategic options at this time. There can be no assurance, however, that this process will result in any such transaction.

Third Quarter 2022 Summary Financial Results

Cash and cash equivalents were $43.9 million as of September 30, 2022, compared to $53.4 million as of December 31, 2021. ARCA believes that its current cash and cash equivalents, will be sufficient to fund its operations at the current levels through at least the end of 2023. The Company’s review of its strategic options may impact this projection.

Research and development (R&D) expenses were $1.0 million for the quarter ended September 30, 2022, compared to $3.4 million for the corresponding period in 2021. In the third quarter of 2022, ARCA implemented a strategic reduction of the workforce and recorded total restructuring charges of approximately $0.8 million, of which $0.5 million and $0.3 million were recognized in research and development and general and administrative expenses, respectively, in connection with the restructuring, all in the form of one-time termination benefits. The $2.4 million decrease in R&D expenses in the third quarter was primarily related to the completion of enrollment in the rNAPc2 Phase 2b clinical trial in the fourth quarter of 2021, partially offset by the restructuring charges discussed above. R&D expenses in 2022 are expected to be lower than 2021.

General and administrative (G&A) expenses were $1.5 million for the quarter ended September 30, 2022, compared to $1.3 million for the corresponding period in 2021. The $0.2 million increase in G&A expenses was primarily a result of the restructuring charges discussed above. G&A expenses in 2022 are expected to be slightly higher than 2021 as we maintain administrative activities to support our ongoing operations along with the one-time termination benefits recorded in the third quarter 2022.

Total operating expenses for the quarter ended September 30, 2022 were $2.6 million compared to $4.7 million for the third quarter of 2021.

Net loss for the quarter ended September 30, 2022 was $2.3 million, or $0.16 per basic and diluted share, compared to $4.7 million, or $0.33 per basic and diluted share in the third quarter of 2021.