On May 11, 2023 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported plans to share preliminary data from the dose-escalation portion of its ongoing ALKOVE-1 Phase 1/2 clinical trial for NVL-655, a novel ALK-selective inhibitor, in the second half of 2023, and reported first quarter 2023 financial results (Press release, Nuvalent, MAY 11, 2023, View Source [SID1234631528]).

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ALKOVE-1 is a Phase 1/2, multicenter, open-label, dose-escalation and expansion trial evaluating NVL-655 in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors. The Phase 1 dose-escalation portion of the study is enrolling patients with previously treated ALK-positive solid tumors and will evaluate the overall safety and tolerability of NVL-655. Additional objectives include determination of the recommended Phase 2 dose (RP2D), characterization of the pharmacokinetic profile, and evaluation of preliminary anti-tumor activity. Preclinical data, including those presented recently at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, demonstrated that NVL-655 had broad preclinical activity across diverse ALK oncoproteins, single and compound resistance mutations, and tumor types while maintaining strong selectivity for ALK over TRKB and CNS penetrance.

"2023 is a year of focused, data-driven execution towards our goal of delivering a pipeline of novel kinase inhibitors to patients as efficiently as possible," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "We plan to report preliminary data from our ALKOVE-1 trial of NVL-655 for patients with advanced ALK-positive NSCLC and other solid tumors in the second half of the year. We continue to enroll patients in the Phase 1 portion of the ARROS-1 trial of NVL-520 for advanced ROS1-positive NSCLC and other solid tumors in support of RP2D selection, and to advance NVL-330, our novel HER2-selective inhibitor for patients with HER2 exon 20 insertion-positive cancers, through IND-enabling studies. With a solid cash position and an expert team, we are well-positioned to deliver on both our near- and long-term goals."

First Quarter 2023 Financial Results

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Cash Position & Operating Runway: Cash, cash equivalents and marketable securities were $450.5 million as of March 31, 2023. Nuvalent believes the existing cash, cash equivalents and marketable securities are expected to be sufficient to fund its current operating plan into the second half of 2025.
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R&D Expenses: Research and development (R&D) expenses were $22.1 million for the first quarter of 2023.
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G&A Expenses: General and administrative (G&A) expenses were $8.1 million for the first quarter of 2023.
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Net Loss: Net loss for the first quarter of 2023 was $25.2 million, or $0.44 per share.
About NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M ("GRLM"), G1202R / G1269A ("GRGA"), or G1202R/L1198F ("GRLF"). NVL-655 has been optimized for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK 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/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 study (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive NSCLC and other solid tumors.

On May 11, 2023 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported that it will present preliminary data from its Phase 1 dose escalation clinical trial of NKX019 at two upcoming scientific conferences in June 2023: the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Hybrid Congress and the 17TH International Conference on Malignant Lymphoma (17-ICML) (Press release, Nkarta, MAY 11, 2023, View Source [SID1234631527]). NKX019 is an allogeneic, off-the-shelf cell therapy candidate comprising NK cells derived from healthy donors and engineered to target the B-cell antigen CD19.

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The purpose of the presentations is to ensure that clinical investigators and the broader clinical community have the opportunity to assess the NKX019 clinical data from the November 2022 data cut-off in a peer-reviewed format. These data were previously disclosed at a company event in December 2022. Nkarta continues to plan to present an update to these data later in 2023.

European Hematology Association 2023 Hybrid Congress
Oral Presentation: First in Human Data of NKX019, an Allogeneic CAR NK for the Treatment of Relapsed/Refractory (R/R) B-Cell Malignancies
June 10, 2023
Session s437 4:30 p.m. – 5:45 p.m. CEST
Presentation S261
Abstracts are available on the EHA (Free EHA Whitepaper) website.

17TH International Conference on Malignant Lymphoma
Encore Poster Presentation: First in Human Data of NKX019, an Allogeneic CAR NK for the Treatment of Relapsed/Refractory (R/R) B-Cell Malignancies
June 14 – June 16, 2023
Abstract 389
Abstract titles are available on the 17-ICML website.
Abstracts are expected to be available on the ICML website on June 9, 2023 at 5:59 p.m. ET.

The presentations will be made available electronically on the Nkarta website following their delivery at the scheduled scientific sessions.

About NKX019
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced tumor cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal and malignant B cells, and it is a validated target for B cell cancer therapies. To learn more about the NKX019 clinical trial in adults with advanced B cell malignancies, please visit ClinicalTrials.gov.

On May 11, 2023 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported that it will present preliminary data from its Phase 1 dose escalation clinical trial of NKX019 at two upcoming scientific conferences in June 2023: the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Hybrid Congress and the 17TH International Conference on Malignant Lymphoma (17-ICML) (Press release, Nkarta, MAY 11, 2023, View Source [SID1234631526]). NKX019 is an allogeneic, off-the-shelf cell therapy candidate comprising NK cells derived from healthy donors and engineered to target the B-cell antigen CD19.

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The purpose of the presentations is to ensure that clinical investigators and the broader clinical community have the opportunity to assess the NKX019 clinical data from the November 2022 data cut-off in a peer-reviewed format. These data were previously disclosed at a company event in December 2022. Nkarta continues to plan to present an update to these data later in 2023.

European Hematology Association 2023 Hybrid Congress
Oral Presentation: First in Human Data of NKX019, an Allogeneic CAR NK for the Treatment of Relapsed/Refractory (R/R) B-Cell Malignancies
June 10, 2023
Session s437 4:30 p.m. – 5:45 p.m. CEST
Presentation S261
Abstracts are available on the EHA (Free EHA Whitepaper) website.

17TH International Conference on Malignant Lymphoma
Encore Poster Presentation: First in Human Data of NKX019, an Allogeneic CAR NK for the Treatment of Relapsed/Refractory (R/R) B-Cell Malignancies
June 14 – June 16, 2023
Abstract 389
Abstract titles are available on the 17-ICML website.
Abstracts are expected to be available on the ICML website on June 9, 2023 at 5:59 p.m. ET.

The presentations will be made available electronically on the Nkarta website following their delivery at the scheduled scientific sessions.

About NKX019

NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced tumor cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal and malignant B cells, and it is a validated target for B cell cancer therapies. To learn more about the NKX019 clinical trial in adults with advanced B cell malignancies, please visit ClinicalTrials.gov.

On May 11, 2023 NeuBase Therapeutics, Inc. (Nasdaq: NBSE) ("NeuBase" or the "Company"), a biotechnology company developing Stealth Editors to perform in vivo gene editing without triggering the immune system, reported its financial results for the three-month period ended March 31, 2023 and other recent developments (Press release, NeuBase Therapeutics, MAY 11, 2023, View Source [SID1234631525]).

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"To date in 2023, we have made steady progress advancing the development of our gene editing application based on our PATrOL platform. One of the main drivers behind the initial success of this application area, and speed at which we are moving forward, is the ability to leverage our extensive experience in peptide nucleic acids ("PNAs"), the chemistry which forms the core of our platform. PNAs have been shown to engage the double-stranded human genome due to their high binding affinity and exquisite sequence selectivity. This chemistry would allow us to tag a locus in the genome that harbors a mutation with a simple synthetic compound and recruit the cell’s own machinery to repair the mutation. This is the approach behind our in vivo gene editing platform," stated Dietrich A. Stephan, Ph.D., Founder and Chief Executive Officer of NeuBase. "We believe our Stealth Editors can potentially address up to 90% of disease-causing mutations, compared to the estimated approximately 20% addressed by base editing platforms currently in development. In addition, our approach to gene editing offers several benefits that differentiate us from CRISPR/Cas editors, base editors, and prime editors. For example, Stealth Editors are non-immunogenic and have exquisite fidelity, maximizing the ability to re-dose should durability wane over time, which is a situation we have seen with gene therapy approaches in the past."

"Throughout the remainder of the year we look forward to presenting initial ex vivo and in vivo editing results against high-value genetic mutations, together with associated performance metrics, such as fidelity and efficiency. This includes preclinical data in two oral presentations the NeuBase team will provide at the ASGCT (Free ASGCT Whitepaper) 26th Annual Meeting taking place next week. We plan to follow up the presentations with an investor and analyst conference call on May 22, 2023 to discuss these data," concluded Dr. Stephan.

First Quarter of 2023 and Recent Operating Highlights

Gene Editing Program:

The Company is advancing development of the differentiated gene editing capabilities of its PATrOL platform and development of Stealth Editors.
Two abstracts accepted for oral presentations at the ASGCT (Free ASGCT Whitepaper) 26th Annual Meeting, which is being held in Los Angeles, CA and virtually on May 16-20, 2023. Management plans to hold an investor and analyst conference call on May 22, 2023.

Details of the gene editing pipeline expected to be provided during 2023.
Gene Editing Research Agreements:
The Company’s previously announced collaboration with a global healthcare company to evaluate the PATrOL platform for three monogenic genetic diseases remains on track. The global healthcare company will have the exclusive opportunity, subject to certain terms and conditions, to license and develop the drug candidates created under this research evaluation agreement.
Engaged in discussions with other healthcare companies on the potential for additional research agreements.
Gene Silencing Pipeline Collaborations:
NeuBase continued active pursuit of collaborative initiatives, including partnerships, for the Company’s myotonic dystrophy type 1, Huntington’s disease, and KRAS (G12D and G12V) programs. The Company currently expects that any collaborations that could result from these discussions would be announced in the second half of 2023.
Financial Results for the Quarter Ended March 31, 2023

As of March 31, 2023, the Company had cash and cash equivalents of approximately $13.8 million, compared with approximately $17.4 million as of December 31, 2022.
NeuBase estimates its current cash and cash equivalents are sufficient to fund currently planned operating and capital expenditures into the second quarter of 2024.

For the quarter ended March 31, 2023, the Company reported a net loss of approximately $4.1 million, or a net loss of $0.12 per share, compared with a net loss of approximately $9.9 million, or a net loss of $0.30 per share, for the same period last year.

For the quarter ended March 31, 2023, total operating expenses were approximately $4.2 million, consisting of approximately $2.9 million in general and administrative expenses and $1.3 million in research and development expenses. This compares with total operating expenses of approximately $9.9 million for the same period last year, consisting of approximately $3.1 million in general and administrative expenses and $6.8 million in research and development expenses.

On April 21, 2023, the Company’s Board of Directors approved a change in its fiscal year from the twelve months beginning October 1 and ending September 30 to the twelve months beginning January 1 and ending December 31, which will be effective for the year ending December 31, 2023.

On May 11, 2023 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported business highlights and financial results for the quarter ended March 31, 2023 (Press release, Monte Rosa Therapeutics, MAY 11, 2023, View Source [SID1234631524]).

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"During the first quarter, we made significant progress with our Phase 1/2 clinical trial of MRT-2359 in MYC-driven solid tumors. This trial continues to attract top oncologists and academic centers, and patient enrollment is on track for us to have initial data to share in the second half of the year. We remain excited about the prospect of bringing a potential therapeutic option to a range of indications driven by MYC, one of the most frequently altered families of oncogenes," said Markus Warmuth, M.D., CEO of Monte Rosa. "Furthermore, we expect to declare a development candidate in our VAV1 program in the second quarter. This milestone will mark a significant advancement in our pipeline of MGD-based medicines in the field of immunology and inflammation. We believe the underlying biology and our preclinical data support the potential of our VAV1-directed MGD to provide clinical benefit in multiple autoimmune diseases. Our continued progress with our pipeline speaks to the power of our QuEEN discovery engine and our position as a leading molecular glue degrader company. Backed by a strong balance sheet and a sharp focus on developing impactful medicines, we look forward to continuing to further the development of our molecular glue therapeutics."

FIRST QUARTER 2023 AND RECENT HIGHLIGHTS

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Presented preclinical data highlighting the preferential activity of MRT-2359, an orally bioavailable GSPT1-directed MGD, in MYC-driven tumor cells at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando, FL
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Appointed Jan Skvarka, Ph.D., MBA, an accomplished biopharmaceutical executive with extensive operational, strategic, and financial expertise to the Company’s Board of Directors

UPCOMING MILESTONES

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On track to announce initial clinical data, including pharmacokinetic (PK), pharmacodynamic (PD), safety, and available initial efficacy data from the Phase 1 part of the ongoing Phase 1/2 clinical trial evaluating MRT-2359 in MYC-driven tumors, including non-small cell lung cancer, small cell lung cancer, and other MYC-driven tumors, in the second half of 2023
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On track to advance multiple preclinical programs to development candidates in immunology, inflammation, and oncology, including declaring a VAV1 development candidate in the second quarter of 2023

FIRST QUARTER 2023 FINANCIAL RESULTS

Research and Development (R&D) Expenses: R&D expenses for the first quarter of 2023 were $26.8 million, compared to $17.9 million for the first quarter of 2022. These increases were driven by the successful achievement of key milestones in our R&D organization, including the advancement of MRT-2359 in the clinic, the progression of our preclinical pipeline in lead optimization, and the continued development of the Company’s QuEEN platform for discovery efforts. The increase in R&D expenses was driven by increased headcount and laboratory-related expenses to achieve these milestones. Non-cash stock-based compensation constituted $2.1 million of R&D expenses for Q1 2023, compared to $1.2 million in the same period in 2022.

General and Administrative (G&A) Expenses: G&A expenses for the first quarter of 2023 were $7.5 million compared to $6.4 million for the first quarter of 2022. The increase in G&A expenses was a result of increased headcount and expenses in support of the company’s growth and operations as a public company. G&A expenses included non-cash stock-based compensation of $1.8 million for the first quarter of 2023, compared to $1.1 million for the same period in 2022.

Net Loss: Net loss for the first quarter of 2023 was $32 million, compared to $23.9 million for the first quarter of 2022.

Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash, and marketable securities as of March 31, 2023, were $237 million, compared to cash, cash equivalents, and restricted cash of $268.1 million as of December 31, 2022. The decrease of $31.1 million was primarily related to cash used to fund operations in the first quarter, including a seasonal reduction in accrued expenses. The company expects that its cash and cash equivalents will be sufficient to fund currently planned operations and capital expenditures into 2025.

About MRT-2359

MRT-2359 is a potent, selective and orally bioavailable molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon and the translation termination factor GSPT1, leading to the targeted degradation of GSPT1 protein. The MYC transcription factors (c‑MYC, L-MYC and N-MYC) are well-established drivers of human cancers that maintain high levels of protein translation, which is critical for uncontrolled cell proliferation and tumor growth. Preclinical studies have shown that this addiction to MYC-induced protein translation creates a dependency on GSPT1. By inducing degradation of GSPT1, MRT-2359 exploits this vulnerability, disrupting the protein synthesis machinery, leading to anti-tumor activity in MYC-driven tumors.

About VAV1

VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T and B cell receptors, whose expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity in vitro and in vivo, as displayed by a significant decrease in cytokine secretion, as well as activity in preclinical models of immune diseases. VAV1-directed MGDs have the potential to provide therapeutic benefits in multiple autoimmune indications, such as multiple sclerosis, rheumatoid arthritis, and dermatological disorders.